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Matozzo V, Brunelli N, Cima F. The underrated immune role of bivalve 'serous cells': New insight from inflammatory responses of the Manila clam Ruditapes philippinarum. FISH & SHELLFISH IMMUNOLOGY 2025; 159:110188. [PMID: 39938623 DOI: 10.1016/j.fsi.2025.110188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 02/07/2025] [Accepted: 02/09/2025] [Indexed: 02/14/2025]
Abstract
This study investigated the immune role of serous cells from the bivalve Ruditapes philippinarum. Histochemical and immunohistochemical assays revealed that the serous cells contained large cytoplasmic vacuoles rich in heparinoid molecules. Heparin and histamine were detected within vacuoles, with distinct spatial distributions, and histoenzymatic assays for serine proteases revealed both tryptase and chymase activity. These findings, together with membrane immunolabelling for c-kit, suggest similarities with vertebrate mast cells. After in vivo bacterial inoculation, serous cells first accumulated at the injury site within 12 h, and 15 h after in vitro treatment, a significant increase in the percentage of serous cells was observed in bacteria-treated samples, supporting targeted responses of proliferation and differentiation following bacterial challenge. Serous cells also underwent marked degranulation following bacterial stimulation, and aggregates of granulocytes, hyalinocytes and serous cells appeared within 1 h of treatment. Extracellular trap formation (ETosis), which is rich in degranulated serous cells and trapped dying bacteria, was observed after 15 h. Serous cells showed nuclear envelope loss and chromatin fragmentation. The extracellular nets were primarily composed of fragmented chromatin and amyloid fibrils forming a scaffold of woven fibres, to which the adhesion of heparin, histamine, and serine proteases occurred after their release into the extracellular environment. To our knowledge, this is the first study that highlights the important role of serous cells in the immune response of bivalves and provides new perspectives for future investigations into the modulation of the inflammatory process.
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Affiliation(s)
| | | | - Francesca Cima
- Department of Biology, University of Padova, Padova, Italy.
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2
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Grinat J, Shriever NP, Christophorou MA. Fantastic proteins and where to find them - histones, in the nucleus and beyond. J Cell Sci 2024; 137:jcs262071. [PMID: 39704565 PMCID: PMC11827605 DOI: 10.1242/jcs.262071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024] Open
Abstract
Animal genomes are packaged into chromatin, a highly dynamic macromolecular structure of DNA and histone proteins organised into nucleosomes. This accommodates packaging of lengthy genomic sequences within the physical confines of the nucleus while also enabling precise regulation of access to genetic information. However, histones existed before chromatin and have lesser-known functions beyond genome regulation. Most notably, histones are potent antimicrobial agents, and the release of chromatin to the extracellular space is a defence mechanism nearly as ancient and widespread as chromatin itself. Histone sequences have changed very little throughout evolution, suggesting the possibility that some of their 'non-canonical' functions are at play in parallel or in concert with their genome regulatory functions. In this Review, we take an evolutionary perspective of histone, nuclear chromatin and extracellular chromatin biology and describe the known extranuclear and extracellular functions of histones. We detail molecular mechanisms of chromatin release and extracellular chromatin sensing, and we discuss their roles in physiology and disease. Finally, we present evidence and give a perspective on the potential of extracellular histones to act as bioactive, cell modulatory factors.
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Kumra Ahnlide J, Thelaus L, Kahn F, van Breda S, Nordenfelt P. NETQUANT2: automated web-based quantification of neutrophil extracellular traps from fluorescence microscopy. Front Immunol 2024; 15:1459933. [PMID: 39697340 PMCID: PMC11652487 DOI: 10.3389/fimmu.2024.1459933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 11/12/2024] [Indexed: 12/20/2024] Open
Abstract
Neutrophil extracellular traps (NETs) are structures that neutrophils form in response to various stimuli, including invading pathogens. NETs are increasingly studied, and their importance has been demonstrated in autoimmunity and infection. However, no consensus has emerged on their quantification, with many studies resorting to manually counting NETs in microscopy images. NETQUANT is a free software for the automated quantification of neutrophil extracellular traps in fluorescence microscopy images. By employing automated image analysis based on biologically relevant criteria for defining NETs, NETQUANT eliminates user bias and reduces analysis time. Despite these advantages, NETQUANT has not reached widespread adoption, partly due to its dependence on proprietary software and challenges associated with local program setup, which has hindered its appeal. Here, we present NETQUANT2, an improved version based on the principles of NETQUANT, released as a web-based software for fast, simple, and unbiased NET quantification from microscopy images. The software guides researchers by displaying relevant morphological data from their sample and allows researchers to interactively configure the analysis, immediately seeing the impact on the result. NETQUANT2 further improves NETQUANT by enabling easy sharing and reusing of configurations and results and enhanced configuration options to handle complex samples better. We believe that the improved accessibility of NETQUANT2 will lead to better reproducibility in NET research and open the field to more researchers while keeping the quality of analysis high.
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Affiliation(s)
- Johannes Kumra Ahnlide
- Department of Clinical Sciences Lund, Infection Medicine, Faculty of Medicine, Lund University, Lund, Sweden
| | - Louise Thelaus
- Department of Clinical Sciences Lund, Infection Medicine, Faculty of Medicine, Lund University, Lund, Sweden
| | - Fredrik Kahn
- Department of Clinical Sciences Lund, Infection Medicine, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Infection Medicine, Skåne University Hospital, Lund, Sweden
| | - Shane van Breda
- Department of Biomedicine, Laboratory for Experimental Rheumatology, University Hospital Basel, Basel, Switzerland
| | - Pontus Nordenfelt
- Department of Clinical Sciences Lund, Infection Medicine, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Laboratory Medicine, Clinical Microbiology, Skåne University Hospital, Lund, Sweden
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Badami GD, Tamburini B, Mohammadnezhad L, Vaz-Rodrigues R, La Barbera L, de la Fuente J, Sireci G. Netosis and trained immunity in tick-borne diseases: a possible pathogenetic role. Cell Immunol 2024; 405-406:104881. [PMID: 39368167 DOI: 10.1016/j.cellimm.2024.104881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/30/2024] [Accepted: 09/30/2024] [Indexed: 10/07/2024]
Abstract
Various types of pathogens transmitted by ticks elicit distinct immune responses just like the emerging α-Gal syndrome that is associated with allergic reactions to tick bites. The mechanisms of Neutrophil Extracellular Traps release (called NETosis) and trained immunity in response to tick-borne microbes have not been extensively investigated. In our paper, we explored the intricate interplay of NETosis and trained immunity within the realm of infectious diseases triggered by tick bites and their possible pathogenetic role in autoimmunity. We conducted an extensive literature search to identify studies for this review, considering articles and reviews published in English within the last years. Additionally, we scrutinized the references of all included papers and relevant review articles to ensure comprehensive coverage. We shed light on a plausible correlation between these innate immune responses and their potential implication in certain pathological conditions, with a specific focus on some autoimmune diseases. These findings offer new perspectives for a more profound comprehension of the immunopathogenesis of certain autoimmune-like signs where clinicians should include Tick-Borne Diseases (TBDs) in their differential diagnoses, in those geographical areas of tick infestation.
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Affiliation(s)
- Giusto Davide Badami
- CLADIBIOR, Department of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, Italy
| | - Bartolo Tamburini
- CLADIBIOR, Department of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, Italy; Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy
| | - Leila Mohammadnezhad
- CLADIBIOR, Department of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, Italy; Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy
| | - Rita Vaz-Rodrigues
- SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13071 Ciudad Real, Spain
| | - Lidia La Barbera
- Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy
| | - José de la Fuente
- SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13071 Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater OK 74078, USA
| | - Guido Sireci
- CLADIBIOR, Department of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, Italy.
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Dusch A, Segeritz L, Henrich M, Taubert A, Hermosilla C. Organ Tropism of Angiostrongylus vasorum Larval Stages in Infected African Giant Snails ( Lissachatina fulica). Pathogens 2024; 13:946. [PMID: 39599499 PMCID: PMC11597215 DOI: 10.3390/pathogens13110946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 10/14/2024] [Accepted: 10/24/2024] [Indexed: 11/29/2024] Open
Abstract
Angiostrongylus vasorum is a metastrongyloid lungworm causing severe cardiovascular disease in domestic and wild animals. During its heteroxenous life cycle, A. vasorum requires obligate gastropod intermediate hosts. Little is known about A. vasorum larval organ tropism and development in gastropod intermediate hosts. Thus, the aim of this study was to analyze in vivo development of A. vasorum larval stages in experimentally infected African giant snails (Lissachatina fulica). Adult L. fulica (n = 26) were orally infected with A. vasorum-L1 and thereafter continuously euthanized. Gastropod organs were artificially digested and microscopically analyzed for the presence of A. vasorum larvae. Moreover, paraffin-fixed organs were investigated histologically for snail-borne innate immune response. In the current study, the success of L. fulica oral infection was demonstrated, thereby reaching larval recovery rates of up to 49.7%. During snail infection, an organ tropism of A. vasorum larvae was detected for the lungs and the foot muscular tissue. Overall, A. vasorum-driven gastropod innate immune reactions against larvae varied greatly. In some specimens, larvae were found effectively ensnared by recruited hemocytes, resulting in granuloma formation, whilst in others, hemocyte-mediated reactions were barely observed. Nevertheless, these evidences demand more studies on hemocyte-derived effector mechanisms against A. vasorum.
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Affiliation(s)
- Alena Dusch
- Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen, 35392 Giessen, Germany; (L.S.); (A.T.); (C.H.)
| | - Lisa Segeritz
- Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen, 35392 Giessen, Germany; (L.S.); (A.T.); (C.H.)
| | - Manfred Henrich
- Institute of Pathology, Justus Liebig University Giessen, 35392 Giessen, Germany;
| | - Anja Taubert
- Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen, 35392 Giessen, Germany; (L.S.); (A.T.); (C.H.)
| | - Carlos Hermosilla
- Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen, 35392 Giessen, Germany; (L.S.); (A.T.); (C.H.)
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Lv X, Han Y, Li Y, Wang X, Zhang T, Wang X, Zhang Q, Yang D, Zhao J. Nonylphenol displays immunotoxicity by triggering hemocyte extracellular traps in Manila clam via ROS burst, ERK pathway and glycolysis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 285:117145. [PMID: 39357378 DOI: 10.1016/j.ecoenv.2024.117145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 09/28/2024] [Accepted: 09/30/2024] [Indexed: 10/04/2024]
Abstract
Nonylphenol (NP), an endocrine disruptor, has been demonstrated to be a harmful environmental contaminant and toxic to organisms. In this study, to address concerns regarding the immunotoxicity of NP, we treated clam Ruditapes philippinarum hemocytes with NP in vitro and explored the underlying mechanisms of NP-induced extracellular traps (ETs). NP could induce the formation of hemocytes ETs in a dose-dependent manner. Transcriptomics analysis revealed changes of signaling pathway involved in immunity and energy metabolism in hemocytes after NP stimulation. In this process, both reactive oxygen species (ROS) and myeloperoxidase (MPO) were up-regulated. Moreover, mitogen-activated protein kinase (MAPK) signaling pathway was proved to be activated in the formation of NP-induced ETs, manifested as enhanced phosphorylation of extracellular signal-regulated kinase (ERK) but not p38 or c-Jun N-terminal kinase (JNK). In the presence of U0126, an ERK phosphorylation inhibitor, the NP-induced expression of NADPH oxidase enzyme (NOX) was significantly decreased, which further alleviated the ROS production and ultimately limited the release of ETs. NP exposure increased glucose uptake, along with enhanced activities of glycolysis-related enzymes such as hexokinase (HK) and pyruvate kinase (PK). After inhibiting glycolysis by the inhibitor 2-DG, the formation of NP-induced ETs was significantly suppressed. ERK could regulate mTOR signaling and the PI3K/AKT pathway, potentially directing ETs formation by orchestrating the glycolysis through the activation of key transcription factors c-Myc and HIF-1α. Collectively, the results preliminary confirm that the ERK-NOX-ROS axis and glycolysis are involved in NP-induced ETs formation, contributing to the cellular immunotoxicity in clam.
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Affiliation(s)
- Xiaojing Lv
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China
| | - Yijing Han
- School of Fisheries, Ludong University, Yantai 264025, PR China
| | - Yongxue Li
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China
| | - Xin Wang
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China
| | - Tianyu Zhang
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China
| | - Xiaodan Wang
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China
| | - Qianqian Zhang
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China
| | - Dinglong Yang
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China.
| | - Jianmin Zhao
- Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, PR China; Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China.
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7
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Walt HK, Bronzato-Badial A, Maedo SE, Hinton JA, King JG, Pietri JE, Hoffmann FG. Under the radar: Transcriptomic responses of bed bugs to an entomopathogen, environmental bacteria, and a human pathogen. J Invertebr Pathol 2024; 206:108182. [PMID: 39178984 DOI: 10.1016/j.jip.2024.108182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/14/2024] [Accepted: 08/20/2024] [Indexed: 08/26/2024]
Abstract
Bed bugs (Hemiptera: Cimicidae) are widely distributed, obligately blood-feeding insects, but they have never been linked to pathogen transmission in humans. Most other hematophagous insects that frequently bite humans transmit pathogens, and it is unclear why bed bugs do not. One hypothesis is that bed bugs have evolved a highly robust immune system because their mating system, traumatic insemination, exposes females to consistent wounding and bacterial infections. Although this has been proposed, very little is known about the bed bug immune system and how bed bugs respond to microbial challenges introduced by wounding. Similarly, there is little known about how the bed bug immune system responds to human pathogens. Understanding the bed bug immune system could give insight to why bed bugs appear not to transmit disease and under what circumstances they could, while also facilitating biological control efforts involving microbes. To investigate the transcriptomic response of bed bugs to immune challenges, we exposed female bed bugs to three bacterial challenges. 1.) Pseudomonas fluorescens, an entomopathogen known to have harmful effects to bed bugs, 2.) bacteria cultured from a bed bug enclosure (99.9 % Bacillus spp.), likely encountered during traumatic insemination, and 3.) Borrelia duttoni, a human vector-borne pathogen that causes relapsing fever. We compared the transcriptomes of infected bed bugs with uninfected matched controls in a pairwise fashion, focusing on immune-related genes. We found many known antimicrobial effector genes upregulated in response to P. fluorescens and traumatic insemination-associated bacteria, but interestingly, not in response to B. duttoni. In the differentially expressed genes that were shared between experiments, we found significant overlap in the P. fluorescens treatment and the traumatic insemination bacteria treatment, and between the P. fluorescens and B. duttoni treatments, but not between the traumatic insemination bacteria treatment and the B. duttoni treatment. Finally, we identify previously overlooked candidates for future studies of immune function in bed bugs, including a peroxidase-like gene, many putative cuticle-associated genes, a laccase-like gene, and a mucin-like gene. By taking a comprehensive transcriptomic approach, our study is an important step in understanding how bed bugs respond to diverse immune challenges.
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Affiliation(s)
- Hunter K Walt
- Department of Biochemistry, Nutrition, and Health Promotion, Mississippi State University, Mississippi State, MS, USA
| | - Aline Bronzato-Badial
- Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University, Mississippi State, MS, USA
| | - Sophie E Maedo
- Department of Biochemistry, Nutrition, and Health Promotion, Mississippi State University, Mississippi State, MS, USA
| | - Joseph A Hinton
- Department of Biochemistry, Nutrition, and Health Promotion, Mississippi State University, Mississippi State, MS, USA
| | - Jonas G King
- Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University, Mississippi State, MS, USA
| | - Jose E Pietri
- Sanford School of Medicine, Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, SD, USA.
| | - Federico G Hoffmann
- Department of Biochemistry, Nutrition, and Health Promotion, Mississippi State University, Mississippi State, MS, USA; Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS, USA.
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Wu S, Cai B, Wang T, Cao Z, Peng H, Liu H. Eosinophil extracellular traps in respiratory ailment: Pathogenic mechanisms and clinical translation. World J Otorhinolaryngol Head Neck Surg 2024; 10:213-224. [PMID: 39233861 PMCID: PMC11369806 DOI: 10.1002/wjo2.138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 08/07/2023] [Accepted: 08/10/2023] [Indexed: 09/06/2024] Open
Abstract
Background Eosinophilic extracellular traps (EETs) are reticular complexes comprising deoxyribonucleic-Acid (DNA) fibers and granule proteins. Aims EETs play a crucial role in antimicrobial host responses and are pathogenic when overproduced or under degraded. EETs created by eosinophils appear to enable vital immune responses against extra-cellular pathogens, nevertheless, trap overproduction is evident in pathology. Materials & Methods As considerably research is performed, new data affirmed that EETs can alter the outcome of respiratory ailment. Results We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation. Discussion Whether EETs can be used as a prospective brand-new target for the diagnosis, treatment and prognosis of respiratory ailments is a scientific theme worth studying. Conclusion We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation.
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Affiliation(s)
- Shun‐Yu Wu
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Bo‐Yu Cai
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Tian‐Yu Wang
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Zhi‐Wen Cao
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Hu Peng
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Huan‐Hai Liu
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
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Poland CA, Duffin R, Weber K, Dekant W, Borm PJA. Is pulmonary inflammation a valid predictor of particle induced lung pathology? The case of amorphous and crystalline silicas. Toxicol Lett 2024; 399 Suppl 1:18-30. [PMID: 37454774 DOI: 10.1016/j.toxlet.2023.07.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 07/10/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023]
Abstract
Although inflammation is a normal and beneficial response, it is also a key event in the pathology of many chronic diseases, including pulmonary and systemic particle-induced disease. In addition, inflammation is now considered as the key response in standard settings for inhaled particles and a critical endpoint in OECD-based sub-acute/ chronic animal inhalation testing protocols. In this paper, we discuss that whilst the role of inflammation in lung disease is undeniable, it is when inflammation deviates from normal parameters that adversity occurs. We introduce the importance of the time course and in particular, the reversibility of inflammation in the progression towards tissue remodelling and neoplastic changes as commonly seen in rat inhalation studies. For this purpose, we used sub-chronic/ chronic studies studies with synthetic amorphous silicas (SAS) and reactive crystalline silica (RCS) as a source of data to describe the time-course of inflammation towards and beyond adversity. Whilst amorphous silicas induce an acute but reversible inflammatory response, only RCS induces a persistent, progressive response after cessation of exposure, resulting in fibrosis and carcinogenicity in rodents and humans. This suggests that the use of inflammation as a fixed endpoint at the cessation of exposure may not be a reliable predictor of particle-induced lung pathology. We therefore suggest extending the current OECD testing guidelines with a recovery period, that allows inflammation to resolve or progress into altered structure and function, such as fibrosis.
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Affiliation(s)
- Craig A Poland
- Regulatory Compliance Limited, 6 Dryden Road, Loanhead, Midlothian EH20 9TY, UK; Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
| | - Rodger Duffin
- Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Klaus Weber
- AnaPath Services GmbH, Hammerstrasse 49, 4410 Liestal, Switzerland
| | - Wolfgang Dekant
- Department of Toxicology, University of Würzburg, Rhönstrasse 9, 97080 Würzburg, Germany
| | - Paul J A Borm
- Nanoconsult, Grindakker 10, Spaubeek, The Netherlands
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Ma Z, Wu Y, Zhang Y, Zhang W, Jiang M, Shen X, Wu H, Chen X, Di G. Morphologic, cytometric, quantitative transcriptomic and functional characterisation provide insights into the haemocyte immune responses of Pacific abalone ( Haliotis discus hannai). Front Immunol 2024; 15:1376911. [PMID: 39015569 PMCID: PMC11250055 DOI: 10.3389/fimmu.2024.1376911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/31/2024] [Indexed: 07/18/2024] Open
Abstract
In recent years, the abalone aquaculture industry has been threatened by the bacterial pathogens. The immune responses mechanisms underlying the phagocytosis of haemocytes remain unclear in Haliotis discus hannai. It is necessary to investigate the immune mechanism in response to these bacterial pathogens challenges. In this study, the phagocytic activities of haemocytes in H. discus hannai were examined by flow cytometry combined with electron microscopy and transcriptomic analyses. The results of Vibrio parahaemolyticus, Vibrio alginolyticus and Staphylococcus aureu challenge using electron microscopy showed a process during phagosome formation in haemocytes. The phagocytic rate (PP) of S. aureus was higher than the other five foreign particles, which was about 63%. The PP of Vibrio harveyi was about 43%, the PP peak of V. alginolyticus in haemocyte was 63.7% at 1.5 h. After V. parahaemolyticus and V. alginolyticus challenge, acid phosphatase, alkaline phosphatase, total superoxide dismutase, lysozyme, total antioxidant capacity, catalase, nitric oxide synthase and glutathione peroxidase activities in haemocytes were measured at different times, differentially expressed genes (DEGs) were identified by quantitative transcriptomic analysis. The identified DEGs after V. parahaemolyticus challenge included haemagglutinin/amebocyte aggregation factor-like, supervillin-like isoform X4, calmodulin-like and kyphoscoliosis peptidase-like; the identified DEGs after V. alginolyticus challenge included interleukin-6 receptor subunit beta-like, protein turtle homolog B-like, rho GTPase-activating protein 6-like isoform X2, leukocyte surface antigen CD53-like, calponin-1-like, calmodulin-like, troponin C, troponin I-like isoform X4, troponin T-like isoform X18, tumor necrosis factor ligand superfamily member 10-like, rho-related protein racA-like and haemagglutinin/amebocyte aggregation factor-like. Some immune-related KEGG pathways were significantly up-regulated or down-regulated after challenge, including thyroid hormone synthesis, Th17 cell differentiation signalling pathway, focal adhesion, melanogenesis, leukocyte transendothelial migration, inflammatory mediator regulation of TRP channels, ras signalling pathway, rap1 signalling pathway. This study is the first step towards understanding the H. discus hannai immune system by adapting several tools to gastropods and providing a first detailed morpho-functional study of their haemocytes.
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Affiliation(s)
- Zeyuan Ma
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Yunlong Wu
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Yu Zhang
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Weini Zhang
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Mingmei Jiang
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Xiaoyue Shen
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Hailian Wu
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Xinhua Chen
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
- Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Guilan Di
- State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
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11
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Cho Y, Cho S. Granulocyte dynamics: a key player in the immune priming effects of crickets. Front Immunol 2024; 15:1383498. [PMID: 38827743 PMCID: PMC11140058 DOI: 10.3389/fimmu.2024.1383498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 05/06/2024] [Indexed: 06/04/2024] Open
Abstract
This study investigates immune priming effects associated with granulocytes in crickets through a comprehensive analysis. Kaplan-Meier survival analysis reveals a significant contrast in survival rates, with the heat-killed Bacillus thuringiensis (Bt)-primed group exhibiting an impressive ~80% survival rate compared to the PBS buffer-primed group with only ~10% survival 60 hours post live Bt infection. Hemocyte analysis underscores elevated hemocyte counts, particularly in granulocytes of the killed Bt-primed group, suggesting a correlation between the heat-killed Bt priming and heightened immune activation. Microscopy techniques further explore granulocyte morphology, unveiling distinctive immune responses in the killed Bt-primed group characterized by prolonged immune activation, heightened granulocyte activity, phagocytosis, and extracellular trap formation, contributing to enhanced survival rates. In particular, after 24 hours of injecting live Bt, most granulocytes in the PBS buffer-primed group exhibited extracellular DNA trap cell death (ETosis), while in the killed Bt-primed group, the majority of granulocytes were observed to maintain highly activated extracellular traps, sustaining the immune response. Gene expression analysis supports these findings, revealing differential regulation of immune-related genes such as antibacterial humoral response, detection of bacterial lipopeptides, and cellular response to bacteria lipopeptides. Additionally, the heat-killed Bt-primed group, the heat-killed E. coli-primed group, and the PBS-primed group were re-injected with live Bt 2 and 9 days post priming. Two days later, only the PBS-primed group displayed low survival rates. After injecting live Bt 9 days later, the heat-killed E. coli-primed group surprisingly showed a similarly low survival rate, while the heat-killed Bt-primed group exhibited a high survival rate of ~60% after 60 hours, with actively moving and healthy crickets. In conclusion, this research provides valuable insights into both short-term and long-term immune priming effects in crickets, contributing to our understanding of invertebrate immunity with potential applications in public health.
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Affiliation(s)
- Youngwoo Cho
- Department of Plant Medicine, College of Agriculture and Life Science, Kangwon National University, Chuncheon, Republic of Korea
- Department of Interdisciplinary Program in Smart Agriculture, College of Agriculture and Life Science, Kangwon National University, Chuncheon, Republic of Korea
| | - Saeyoull Cho
- Department of Plant Medicine, College of Agriculture and Life Science, Kangwon National University, Chuncheon, Republic of Korea
- Department of Interdisciplinary Program in Smart Agriculture, College of Agriculture and Life Science, Kangwon National University, Chuncheon, Republic of Korea
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12
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Vandepas LE, Stefani C, Domeier PP, Traylor-Knowles N, Goetz FW, Browne WE, Lacy-Hulbert A. Extracellular DNA traps in a ctenophore demonstrate immune cell behaviors in a non-bilaterian. Nat Commun 2024; 15:2990. [PMID: 38582801 PMCID: PMC10998917 DOI: 10.1038/s41467-024-46807-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 03/08/2024] [Indexed: 04/08/2024] Open
Abstract
The formation of extracellular DNA traps (ETosis) is a first response mechanism by specific immune cells following exposure to microbes. Initially characterized in vertebrate neutrophils, cells capable of ETosis have been discovered recently in diverse non-vertebrate taxa. To assess the conservation of ETosis between evolutionarily distant non-vertebrate phyla, we observed and quantified ETosis using the model ctenophore Mnemiopsis leidyi and the oyster Crassostrea gigas. Here we report that ctenophores - thought to have diverged very early from the metazoan stem lineage - possess immune-like cells capable of phagocytosis and ETosis. We demonstrate that both Mnemiopsis and Crassostrea immune cells undergo ETosis after exposure to diverse microbes and chemical agents that stimulate ion flux. We thus propose that ETosis is an evolutionarily conserved metazoan defense against pathogens.
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Affiliation(s)
- Lauren E Vandepas
- NRC Research Associateship Program, Seattle, WA, USA.
- Northwest Fisheries Science Center, National Oceanographic and Atmospheric Administration, Seattle, WA, 98112, USA.
- Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA.
- Department of Biology, University of Miami, Coral Gables, FL, 33146, USA.
| | - Caroline Stefani
- Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA
| | - Phillip P Domeier
- Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA
| | - Nikki Traylor-Knowles
- Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Miami, FL, 33149, USA
| | - Frederick W Goetz
- Northwest Fisheries Science Center, National Oceanographic and Atmospheric Administration, Seattle, WA, 98112, USA
| | - William E Browne
- Department of Biology, University of Miami, Coral Gables, FL, 33146, USA
| | - Adam Lacy-Hulbert
- Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA
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13
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Tu H, Ren H, Jiang J, Shao C, Shi Y, Li P. Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2306457. [PMID: 38044275 PMCID: PMC10885667 DOI: 10.1002/advs.202306457] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/06/2023] [Indexed: 12/05/2023]
Abstract
Neutrophils, accounting for ≈70% of human peripheral leukocytes, are key cells countering bacterial and fungal infections. Neutrophil homeostasis involves a balance between cell maturation, migration, aging, and eventual death. Neutrophils undergo different death pathways depending on their interactions with microbes and external environmental cues. Neutrophil death has significant physiological implications and leads to distinct immunological outcomes. This review discusses the multifarious neutrophil death pathways, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and outlines their effects on immune responses and disease progression. Understanding the multifaceted aspects of neutrophil death, the intersections among signaling pathways and ramifications of immunity will help facilitate the development of novel therapeutic methods.
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Affiliation(s)
- Haiyue Tu
- The First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionInstitutes for Translational MedicineSuzhou Medical College of Soochow UniversitySuzhouJiangsu215123China
| | - Haoyu Ren
- The First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionInstitutes for Translational MedicineSuzhou Medical College of Soochow UniversitySuzhouJiangsu215123China
| | - Junjie Jiang
- The First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionInstitutes for Translational MedicineSuzhou Medical College of Soochow UniversitySuzhouJiangsu215123China
| | - Changshun Shao
- The First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionInstitutes for Translational MedicineSuzhou Medical College of Soochow UniversitySuzhouJiangsu215123China
| | - Yufang Shi
- The First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionInstitutes for Translational MedicineSuzhou Medical College of Soochow UniversitySuzhouJiangsu215123China
| | - Peishan Li
- The First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionInstitutes for Translational MedicineSuzhou Medical College of Soochow UniversitySuzhouJiangsu215123China
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14
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Yadav R, Momin A, Godugu C. DNase based therapeutic approaches for the treatment of NETosis related inflammatory diseases. Int Immunopharmacol 2023; 124:110846. [PMID: 37634446 DOI: 10.1016/j.intimp.2023.110846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 08/19/2023] [Accepted: 08/20/2023] [Indexed: 08/29/2023]
Abstract
Neutrophils are the primary host innate immune cells defending against pathogens. One proposed mechanism by which neutrophils limit pathogen transmission is NETosis, which includes releasing the nuclear content into the cytosol by forming pores in the plasma membrane. The extrusion of cellular deoxyribonucleic acid (DNA) results in neutrophil extracellular traps (NETs) composed of nuclear DNA associated with histones and granule proteins. NETosis is driven by the enzyme PAD-4 (Peptidylarginine deiminase-4), which converts arginine into citrulline, leading to decondensation of chromatin, separation of DNA, and eventual extrusion. DNase is responsible for the breakdown of NETs. On the one hand, the release of DNase may interfere with the antibacterial effects of NETs; further, DNase may protect tissues from self-destruction caused by the increased release of NET under septic conditions. NETs in physiological quantities are expected to have a role in anti-infectious innate immune responses. In contrast, abnormally high concentrations of NETs in the body that are not adequately cleared by DNases can damage tissues and cause inflammation. Through several novel approaches, it is now possible to avoid the adverse effects caused by the continued release of NETs into the extracellular environment. In this review we have highlighted the basic mechanisms of NETosis, its significance in the pathogenesis of various inflammatory disorders, and the role of DNase enzyme with a focus on the possible function of nanotechnology in its management.
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Affiliation(s)
- Rachana Yadav
- Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Alfiya Momin
- Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Chandraiah Godugu
- Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
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15
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Mengal K, Kor G, Siino V, Buřič M, Kozák P, Levander F, Niksirat H. Quantification of proteomic profile changes in the hemolymph of crayfish during in vitro coagulation. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2023; 147:104760. [PMID: 37331675 DOI: 10.1016/j.dci.2023.104760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/20/2023]
Abstract
Hemolymph is the circulatory fluid that fills the body cavity of crustaceans, analogous to blood in vertebrates. Hemolymph coagulation, similar to blood clotting in vertebrates, plays a crucial role in wound healing and innate immune responses. Despite extensive studies on the clotting process in crustaceans, no comparative quantitative analysis of the protein composition of non-clotted and clotted hemolymph in any decapod has been reported. In this study, we used label-free protein quantification with high-resolution mass spectrometry to identify the proteomic profile of hemolymph in crayfish and quantify significant changes in protein abundances between non-clotted and clotted hemolymph. Our analysis identified a total of two-hundred and nineteen proteins in both hemolymph groups. Furthermore, we discussed the potential functions of the top most high and low-abundant proteins in hemolymph proteomic profile. The quantity of most of the proteins was not significantly changed during coagulation between non-clotted and clotted hemolymph, which may indicate that clotting proteins are likely pre-synthesized, allowing for a swift coagulation response to injury. Four proteins still showed abundance differences (p < 0.05, fold change>2), including C-type lectin domain-containing proteins, Laminin A chain, Tropomyosin, and Reverse transcriptase domain-containing proteins. While the first three proteins were down-regulated, the last one was up-regulated. The down-regulation of structural and cytoskeletal proteins may affect the process of hemocyte degranulation needed for coagulation, while the up-regulation of an immune-related protein might be attributed to the phagocytosis ability of viable hemocytes during coagulation.
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Affiliation(s)
- Kifayatullah Mengal
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic.
| | - Golara Kor
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Valentina Siino
- Lund University, Department of Immunotechnology, Medicon Village, House 406, 22387, Lund, Sweden
| | - Miloš Buřič
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Pavel Kozák
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Fredrik Levander
- Lund University, Department of Immunotechnology, Medicon Village, House 406, 22387, Lund, Sweden; National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Lund University, Lund, 223 87, Sweden
| | - Hamid Niksirat
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic.
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16
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Brianik CJ, Bouallagui Y, Allam B. Triploid animals, a potential model for ETosis research: Influence of polyploidy on the formation and efficacy of extracellular traps in the eastern oyster. FISH & SHELLFISH IMMUNOLOGY 2023; 140:108992. [PMID: 37567455 DOI: 10.1016/j.fsi.2023.108992] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/04/2023] [Accepted: 08/08/2023] [Indexed: 08/13/2023]
Abstract
Decondensation and the subsequent release of chromatin from specific immune cells in response to inflammatory stimuli is a highly conserved aspect of the innate immune system and leads to the formation of extracellular traps, observable in nearly all forms of multicellular life. This process is known as ETosis, with the release of DNA and its associated antimicrobial proteins physically capturing and neutralizing pathogens following an infection or tissue damage. Despite the universality of this response, data concerning extracellular traps in non-model organisms is limited, with most invertebrate studies doing little more than proving their existence due to difficulties in stimulation and high interindividual variability in trap production. This study provides a novel, simple, and inexpensive method for the consistent stimulation of extracellular traps in eastern oyster (Crassostrea virginica) hemocytes. Using the methods described in this study, we compared how ploidy impacts the rate, size, and efficacy of extracellular traps. Findings demonstrated that hemocyte extracellular traps were potent antimicrobials against both Gram-positive and Gram-negative bacteria. Furthermore, we provide evidence to suggest that agranulocytes may be the primary ETosis effector cells in C. virginica. This study is the first to describe extracellular traps in C. virginica and highlights the possible benefits of using triploid animals to gain a further understanding of ETosis and the factors that regulate its induction and efficacy.
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Affiliation(s)
- Christopher J Brianik
- School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY, 11790, USA
| | - Younes Bouallagui
- School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY, 11790, USA
| | - Bassem Allam
- School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY, 11790, USA.
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17
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Gallo A, Murano C, Notariale R, Caramiello D, Tosti E, Cecchini Gualandi S, Boni R. Immune and Reproductive Biomarkers in Female Sea Urchins Paracentrotus lividus under Heat Stress. Biomolecules 2023; 13:1216. [PMID: 37627280 PMCID: PMC10452167 DOI: 10.3390/biom13081216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/31/2023] [Accepted: 08/02/2023] [Indexed: 08/27/2023] Open
Abstract
The functioning of the immune and reproductive systems is crucial for the fitness and survival of species and is strongly influenced by the environment. To evaluate the effects of short-term heat stress (HS) on these systems, confirming and deepening previous studies, female sea urchin Paracentrotus lividus were exposed for 7 days to 17 °C, 23 and 28 °C. Several biomarkers were detected such as the ferric reducing power (FRAP), ABTS-based total antioxidant capacity (TAC-ABTS), nitric oxide metabolites (NOx), total thiol levels (TTL), myeloperoxidase (MPO) and protease (PA) activities in the coelomic fluid (CF) and mitochondrial membrane potential (MMP), H2O2 content and intracellular pH (pHi) in eggs and coelomocytes, in which TAC-ABTS and reactive nitrogen species (RNS) were also analyzed. In the sea urchins exposed to HS, CF analysis showed a decrease in FRAP levels and an increase in TAC-ABTS, TTL, MPO and PA levels; in coelomocytes, RNS, MMP and H2O2 content increased, whereas pHi decreased; in eggs, increases in MMP, H2O2 content and pHi were found. In conclusion, short-term HS leads to changes in five out of the six CF biomarkers analyzed and functional alterations in the cells involved in either reproductive or immune activities.
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Affiliation(s)
- Alessandra Gallo
- Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy; (A.G.); (R.N.); (E.T.)
| | - Carola Murano
- Department of Integrative Marine Ecology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy;
| | - Rosaria Notariale
- Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy; (A.G.); (R.N.); (E.T.)
| | - Davide Caramiello
- Unit Marine Resources for Research, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy;
| | - Elisabetta Tosti
- Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy; (A.G.); (R.N.); (E.T.)
| | | | - Raffaele Boni
- Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy; (A.G.); (R.N.); (E.T.)
- Department of Sciences, University of Basilicata, Via dell’Ateneo lucano, 10, 85100 Potenza, Italy
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18
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Morales-Covarrubias MS, Ramírez-Azpilcueta BA, Rodríguez JA, Rosa RD. An in vitro method for the analysis of hemocyte-derived extracellular traps in shrimp. MethodsX 2023; 10:102220. [PMID: 37234938 PMCID: PMC10205528 DOI: 10.1016/j.mex.2023.102220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
The formation of extracellular traps (ETs) is a cell death mechanism relying on the release of nucleic acids in response to different stimuli. More recently, ETs have been recognized as an important cellular immune response since they are able to entrap and kill various microorganisms. The main goal was to describe a methodology to induce and visualize the in vitro formation of ETs by shrimp hemocytes. ETs formation was induced by the incubation of hemocyte monolayers from naïve shrimp (Penaeus vannamei) with a standard dose of Vibrio parahaemolyticus M0905. Following fixation, slides were stained with 4',6-diamidino-2-phenylindole (DAPI) and imaged by fluorescence microscopy. The methodology proposed in this study successfully induced the formation and release of hemocyte-derived ETs in penaeid shrimp. The procedure described here can be used as a novel immune marker to assess shrimp health status.
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Affiliation(s)
- María Soledad Morales-Covarrubias
- Centro de Investigación en Alimentación y Desarrollo A.C., Unidad Mazatlán en Acuicultura y Manejo Ambiental. Avenida Sábalo Cerritos s/n, Mazatlán, Sinaloa C.P. 82100, México
| | - Blanca Alicia Ramírez-Azpilcueta
- Centro de Investigación en Alimentación y Desarrollo A.C., Unidad Mazatlán en Acuicultura y Manejo Ambiental. Avenida Sábalo Cerritos s/n, Mazatlán, Sinaloa C.P. 82100, México
| | - Jenny Antonia Rodríguez
- Centro Nacional de Acuicultura e Investigaciones Marinas (CENAIM), Escuela Superior Politécnica del Litoral (ESPOL), Campus Gustavo Galindro Km 30.5 Vía Perimentral, P.O. Box 09-01-5863, Guayaquil, Ecuador
| | - Rafael Diego Rosa
- Department of Cell Biology, Laboratory of Immunology Applied to Aquaculture, Embryology and Genetics, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil
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19
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Martinez V, Dettleff P, Zamorano P, Galarce N, Borie C, Naish K. Host-pathogen interaction involving cytoskeleton changes as well as non-coding regulation as primary mechanisms for SRS resistance in Atlantic salmon. FISH & SHELLFISH IMMUNOLOGY 2023; 136:108711. [PMID: 37004895 DOI: 10.1016/j.fsi.2023.108711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 03/22/2023] [Accepted: 03/25/2023] [Indexed: 06/19/2023]
Abstract
The salmonid rickettsial syndrome (SRS) is a systemic bacterial infection caused by Piscirickettsia salmonis that generates significant economic losses in Atlantic salmon (Salmo salar) aquaculture. Despite this disease's relevance, the mechanisms involved in resistance against P. salmonis infection are not entirely understood. Thus, we aimed at studying the pathways explaining SRS resistance using different approaches. First, we determined the heritability using pedigree data from a challenge test. Secondly, a genome-wide association analysis was performed following a complete transcriptomic profile of fish from genetically susceptible and resistant families within the challenge infection with P. salmonis. We found differentially expressed transcripts related to immune response, pathogen recognition, and several new pathways related to extracellular matrix remodelling and intracellular invasion. The resistant background showed a constrained inflammatory response, mediated by the Arp2/3 complex actin cytoskeleton remodelling polymerization pathway, probably leading to bacterial clearance. A series of biomarkers of SRS resistance, such as the beta-enolase (ENO-β), Tubulin G1 (TUBG1), Plasmin (PLG) and ARP2/3 Complex Subunit 4 (ARPC4) genes showed consistent overexpression in resistant individuals, showing promise as biomarkers for SRS resistance. All these results together with the differential expression of several long non-coding RNAs show the complexity of the host-pathogen interaction of S. salar and P. salmonis. These results provide valuable information on new models describing host-pathogen interaction and its role in SRS resistance.
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Affiliation(s)
- Victor Martinez
- FAVET-INBIOGEN, Faculty of Veterinary Sciences, University of Chile, Avda. Santa Rosa, 11735, Santiago, Chile.
| | - Phillip Dettleff
- FAVET-INBIOGEN, Faculty of Veterinary Sciences, University of Chile, Avda. Santa Rosa, 11735, Santiago, Chile
| | - Pedro Zamorano
- Cell and Molecular Biology-Genetics Unit, University of Antofagasta, Antofagasta, Chile
| | - Nicolás Galarce
- Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, 8370146, Chile
| | - Consuelo Borie
- Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, 8370146, Chile
| | - Kerry Naish
- School of Aquatic and Fishery Sciences, University of Washington, Seattle, United States
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20
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Rinaldi G, de Haro NÁ, Fernando AJ, Desbois AP, Robb CT, Rossi AG. Fish Erythrocyte Extracellular Traps (FEETs) are an evolutionarily conserved cellular process triggered by different stimuli. FISH & SHELLFISH IMMUNOLOGY 2023; 136:108638. [PMID: 36842638 DOI: 10.1016/j.fsi.2023.108638] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 09/16/2022] [Accepted: 02/22/2023] [Indexed: 06/18/2023]
Abstract
Fish erythrocytes remain nucleated, unlike mammalian erythrocytes that undergo enucleation during maturation. Besides oxygen transport, fish erythrocytes are capable of several immune defence processes and thus these cells are candidates for carrying out ETotic responses. ETosis is an evolutionarily conserved innate immune defence process found in both vertebrates and invertebrates, which involves the extrusion of DNA studded with antimicrobial effector proteins into the extracellular space that traps and kills microorganisms. In this present report, we demonstrate that erythrocytes from Danio rerio (zebrafish) produce ETotic-like responses when exposed to both chemical and physiological inducers of ETosis. Furthermore, erythrocytes from Salmo salar (Atlantic salmon) behaved in a similar way. We have termed these ET-like formations, as Fish Erythrocyte Extracellular Traps (FEETs). Several inducers of mammalian ETosis, such as the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin, induced FEETs. Moreover, we found that FEETs depend on the activation of PKC and generation of mitochondrial reactive oxygen species (mROS). This present report is the first demonstration that fish erythrocytes can exhibit ETotic-like responses, unveiling a previously unknown function, which sheds new light on the innate immune arsenal of these cells.
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Affiliation(s)
- Giulia Rinaldi
- Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, Scotland, UK
| | - Neila Álvarez de Haro
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, FK9 4LA, Scotland, UK
| | - Anuruddika J Fernando
- Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, Scotland, UK
| | - Andrew P Desbois
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, FK9 4LA, Scotland, UK
| | - Calum T Robb
- Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, Scotland, UK
| | - Adriano G Rossi
- Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, Scotland, UK.
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Mengal K, Kor G, Kouba A, Kozák P, Niksirat H. Hemocyte coagulation and phagocytic behavior in early stages of injury in crayfish (Arthropoda: Decapoda) affect their morphology. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2023; 141:104618. [PMID: 36526080 DOI: 10.1016/j.dci.2022.104618] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/12/2022] [Accepted: 12/12/2022] [Indexed: 06/17/2023]
Abstract
Crustacean hemocytes are important mediators of immune functions such as coagulation and phagocytosis. We employed an in situ approach to investigate the ultrastructural behavior of hemocytes during coagulation and phagocytosis in the early stages after injury caused by leg amputation, using transmission electron microscopy technique in marbled crayfish Procambarus virginalis. Hemocytes underwent drastic morphological changes during coagulation. The morphology of the cytoplasmic granules changed from electron-dense to electron-lucent forms in an expanding manner. The transformed granules containing amorphous electron-lucent material were observed to merge and discharge their contents into extracellular space for coagulation. We also observed that the contents of the nucleus participate in the process of coagulation. In addition, leg amputation induced extensive muscle degeneration and necrotic tissues were avidly taken up by the phagocytic hemocytes containing distinct phagosomes. Interestingly, we observed for the first time how the digested contents of phagocytized necrotic tissues are incorporated into granules and other cellular components that change the cell morphology by increasing the granularity of the hemocytes. Nevertheless, the degranulation of hemocytes during coagulation can also reduce their granularity. Given that morphological traits are important criteria for hemocyte classification, these morphological changes that occur during coagulation and phagocytosis must be taken into account.
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Affiliation(s)
- Kifayatullah Mengal
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Golara Kor
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Antonín Kouba
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Pavel Kozák
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic
| | - Hamid Niksirat
- University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, 389 25, Vodňany, Czech Republic.
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22
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Neutrophils in Intestinal Inflammation: What We Know and What We Could Expect for the Near Future. GASTROINTESTINAL DISORDERS 2022. [DOI: 10.3390/gidisord4040025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Neutrophils are short-lived cells that play a crucial role in inflammation. As in other tissues, these polymorphonuclear phagocytes are involved in the intestinal inflammatory response, on the one hand, contributing to the activation and recruitment of other immune cells, but on the other hand, facilitating intestinal mucosa repair by releasing mediators that aid in the resolution of inflammation. Even though these responses are helpful in physiological conditions, excessive recruitment of activated neutrophils in the gut correlates with increased mucosal damage and severe symptoms in patients with inflammatory bowel disease (IBD) and pre-clinical models of colitis. Thus, there is growing interest in controlling their biology to generate novel therapeutic approaches capable of reducing exacerbated intestinal inflammation. However, the beneficial and harmful effects of neutrophils on intestinal inflammation are still controversial. With this review, we summarise and discuss the most updated literature showing how neutrophils (and neutrophil extracellular traps) contribute to developing and resolving intestinal inflammation and their putative use as therapeutic targets.
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Janssen L, Muller HS, Martins VDP. Unweaving the NET: Microbial strategies for neutrophil extracellular trap evasion. Microb Pathog 2022; 171:105728. [PMID: 36028070 DOI: 10.1016/j.micpath.2022.105728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 08/12/2022] [Accepted: 08/15/2022] [Indexed: 11/29/2022]
Abstract
Circa 20 years ago, a new type of defense mechanism was described in neutrophils. At the time, this mechanism corresponded to the extrusion of DNA, associated with histones, granular and cytosolic proteins from the cell and it was produced in response to exposure to pathogens or interleukins. The resulting NET-like structure was described as to entrap and/or kill microbes. However, shortly after the discovery the so-called Neutrophil Extracellular Traps, it was soon noticed and often mentioned in the literature that certain microbes are able to evade NET-mediated entrapment and/or death, to the point where its antimicrobial capacities were questioned, depending on the infection context. In this review, we summarize the diversity of strategies published thus far that viruses, fungi, bacteria and protists employ as to prevent or endure NETs. Moreover, we point to a few perspectives on the matter and a few evolutionary speculations on NETs evasion.
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Affiliation(s)
- Luis Janssen
- Institute of Biological Sciences, Department of Cellular Biology, University of Brasilia, Brasilia, Brazil
| | - Herick Sampaio Muller
- Institute of Biological Sciences, Department of Cellular Biology, University of Brasilia, Brasilia, Brazil
| | - Vicente de Paulo Martins
- Institute of Biological Sciences, Department of Cellular Biology, University of Brasilia, Brasilia, Brazil.
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24
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de Eguileor M, Grimaldi A, Pulze L, Acquati F, Morsiani C, Capri M. Amyloid fil rouge from invertebrate up to human ageing: a focus on Alzheimer Disease. Mech Ageing Dev 2022; 206:111705. [DOI: 10.1016/j.mad.2022.111705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 06/29/2022] [Accepted: 07/02/2022] [Indexed: 10/17/2022]
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25
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Liu ML, Lyu X, Werth VP. Recent progress in the mechanistic understanding of NET formation in neutrophils. FEBS J 2022; 289:3954-3966. [PMID: 34042290 PMCID: PMC9107956 DOI: 10.1111/febs.16036] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/11/2021] [Accepted: 05/24/2021] [Indexed: 01/03/2023]
Abstract
Neutrophils are the most abundant circulating white blood cells and one of the major cell types of the innate immune system. Neutrophil extracellular traps (NETs) are a result of the extracellular release of nuclear chromatin from the ruptured nuclear envelope and plasma membrane. The externalized chromatin is an ancient defense weapon for animals to entrap and kill microorganisms in the extracellular milieu, thus protecting animals ranging from lower invertebrates to higher vertebrates. Although the externalized chromatin has the advantage of acting as anti-infective to protect against infections, extracellular chromatin might be problematic in higher vertebrate animals as they have an adaptive immune system that can trigger further immune or autoimmune responses. NETs and their associated nuclear and/or cytoplasmic components may induce sterile inflammation, immune, and autoimmune responses, leading to various human diseases. Though important in human pathophysiology, the cellular and molecular mechanisms of NET formation (also called NETosis) are not well understood. Given that nuclear chromatin forms the backbone of NETs, the nucleus is the root of the nuclear DNA extracellular traps. Thus, nuclear chromatin decondensation, along with the rupture of nuclear envelope and plasma membrane, is required for nuclear chromatin extracellular release and NET formation. So far, most of the literature focuses on certain signaling pathways, which are involved in NET formation but without explanation of cellular events and morphological changes described above. Here, we have summarized emerging evidence and discuss new mechanistic understanding, with our perspectives, in NET formation in neutrophils.
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Affiliation(s)
- Ming-Lin Liu
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, 19104, USA,Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Xing Lyu
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, 19104, USA,Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA,Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Victoria P. Werth
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, 19104, USA,Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
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26
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Rodriguez C, Vega IA, Castro-Vazquez A. A Dissenters' View on AppleSnail Immunobiology. Front Immunol 2022; 13:879122. [PMID: 35693764 PMCID: PMC9178244 DOI: 10.3389/fimmu.2022.879122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 03/28/2022] [Indexed: 11/13/2022] Open
Abstract
We stand as dissenters against the acceptance of scientific knowledge that has not been built on empirical data. With this in mind, this review synthesizes selected aspects of the immunobiology of gastropods and of apple snails (Ampullariidae) in particular, from morphological to molecular and "omics" studies. Our trip went through more than two centuries of history and was guided by an evo-devo hypothesis: that the gastropod immune system originally developed in the mesenchymal connective tissue of the reno-pericardial complex, and that in that tissue some cells differentiated into hematopoietically committed progenitor cells that integrate constitutive hemocyte aggregations in the reno-pericardial territory, whether concentrated in the pericardium or the kidney in a species-specific manner. However, some of them may be freed from those aggregations, circulate in the blood, and form distant contingent aggregations anywhere in the body, but always in response to intruders (i.e., pathogens or any other immune challenge). After that, we reviewed the incipient immunology of the Ampullariidae by critically revising the findings in Pomacea canaliculata and Marisa cornuarietis, the only ampullariid species that have been studied in this respect, and we attempted to identify the effectors and the processes in which they are involved. Particularly for P. canaliculata, which is by far the most studied species, we ask which hemocytes are involved, in which tissues or organs are integrated, and what cellular reactions to intruders this species has in common with other animals. Furthermore, we wondered what humoral factors could also integrate its internal defense system. Among the cellular defenses, we give an outstanding position to the generation of hemocyte nodules, which seems to be an important process for these snails, serving the isolation and elimination of intruders. Finally, we discuss hematopoiesis in apple snails. There have been contrasting views about some of these aspects, but we envision a hematopoietic system centered in the constitutive hemocyte islets in the ampullariid kidney.
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Affiliation(s)
- Cristian Rodriguez
- IHEM, CONICET, Universidad Nacional de Cuyo, Mendoza, Argentina
- Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina
- Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
| | - Israel A. Vega
- IHEM, CONICET, Universidad Nacional de Cuyo, Mendoza, Argentina
- Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina
- Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
| | - Alfredo Castro-Vazquez
- IHEM, CONICET, Universidad Nacional de Cuyo, Mendoza, Argentina
- Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina
- Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
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27
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Sarnik J, Makowska J. Citrullination good or bad guy? Immunobiology 2022; 227:152233. [DOI: 10.1016/j.imbio.2022.152233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 04/11/2022] [Accepted: 05/21/2022] [Indexed: 11/16/2022]
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Shen W, Oladejo AO, Ma X, Jiang W, Zheng J, Imam BH, Wang S, Wu X, Ding X, Ma B, Yan Z. Inhibition of Neutrophil Extracellular Traps Formation by Cl-Amidine Alleviates Lipopolysaccharide-Induced Endometritis and Uterine Tissue Damage. Animals (Basel) 2022; 12:1151. [PMID: 35565576 PMCID: PMC9100562 DOI: 10.3390/ani12091151] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/17/2022] [Accepted: 04/27/2022] [Indexed: 02/05/2023] Open
Abstract
Endometritis is a common disease that affects the production in dairy cows and leads to severe losses in the dairy industry. Neutrophil extracellular traps (NETs) formation promotes pathogenic invasions of the lumen of the tissue, leading to inflammatory diseases such as mastitis, pancreatitis, and septic infection. However, research that could show the relationship between NETs and endometritis is scarce. Cl-amidine has been shown to ameliorate the disease squealing and clinical manifestation in various disease models. In this study, we investigated the role of NETs in LPS-triggered endometritis in rats and evaluated the therapeutic efficiency of Cl-amidine. An LPS-induced endometritis model in rats was established and found that the formation of NETs can be detected in the rat's uterine tissues in vivo. In addition, Cl-amidine treatment can inhibit NETs construction in LPS-induced endometritis in rats. Myeloperoxidase (MPO) activity assay indicated that Cl-amidine treatment remarkably alleviated the inflammatory cell infiltrations and attenuated the damage to the uterine tissue. The Western blot results indicated that Cl-amidine decreased the expression of citrullinated Histone H3 (Cit-H3) and high-mobility group box 1 protein (HMGB1) protein in LPS-induced rat endometritis. The ELISA test indicated that Cl-amidine treatment significantly inhibited the expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. The NETs were determined by Quant-iTTMPicoGreen dsDNA kit®, which indicated that Cl-amidine significantly inhibited the NETs in rat serum. All results showed that Cl-amidine effectively reduced the expression of Cit-H3 and HMGB1 proteins by inhibiting the formation of NETs, thereby attenuating the inflammatory response to LPS-induced endometritis in rats. Hence, Cl-amidine could be a potential candidate for the treatment of endometritis.
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Affiliation(s)
- Wenxiang Shen
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
- College of Veterinary Medicine, Northwest A&F University, Yangling District, Xianyang 712100, China
| | - Ayodele Olaolu Oladejo
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
- Department of Animal Health Technology, Oyo State College of Agriculture and Technology, Igboora 201103, Nigeria
| | - Xiaoyu Ma
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
- College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010010, China
| | - Wei Jiang
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
| | - Juanshan Zheng
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
- College of Veterinary Medicine, Northwest A&F University, Yangling District, Xianyang 712100, China
| | - Bereket Habte Imam
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
- Department of Veterinary Science, Hamelmalo Agricultural College, Keren P.O. Box 397, Eritrea
| | - Shengyi Wang
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
| | - Xiaohu Wu
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
| | - Xuezhi Ding
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
| | - Baohua Ma
- College of Veterinary Medicine, Northwest A&F University, Yangling District, Xianyang 712100, China
| | - Zuoting Yan
- Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Science, Lanzhou 730050, China; (W.S.); (A.O.O.); (X.M.); (W.J.); (J.Z.); (B.H.I.); (S.W.); (X.W.); (X.D.)
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29
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Huang SUS, O’Sullivan KM. The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Players in Casting Dark Webs. Int J Mol Sci 2022; 23:ijms23073793. [PMID: 35409152 PMCID: PMC8998317 DOI: 10.3390/ijms23073793] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 02/04/2023] Open
Abstract
The first description of a new form of neutrophil cell death distinct from that of apoptosis or necrosis was discovered in 2004 and coined neutrophil extracellular traps "(NETs)" or "NETosis". Different stimuli for NET formation, and pathways that drive neutrophils to commit to NETosis have been elucidated in the years that followed. Critical enzymes required for NET formation have been discovered and targeted therapeutically. NET formation is no longer restricted to neutrophils but has been discovered in other innate cells: macrophages/monocytes, mast Cells, basophils, dendritic cells, and eosinophils. Furthermore, extracellular DNA can also be extruded from both B and T cells. It has become clear that although this mechanism is thought to enhance host defense by ensnaring bacteria within large webs of DNA to increase bactericidal killing capacity, it is also injurious to innocent bystander tissue. Proteases and enzymes released from extracellular traps (ETs), injure epithelial and endothelial cells perpetuating inflammation. In the context of autoimmunity, ETs release over 70 well-known autoantigens. ETs are associated with pathology in multiple diseases: lung diseases, vasculitis, autoimmune kidney diseases, atherosclerosis, rheumatoid arthritis, cancer, and psoriasis. Defining these pathways that drive ET release will provide insight into mechanisms of pathological insult and provide potential therapeutic targets.
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30
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Ding Z, Du F, Rönnow CF, Wang Y, Rahman M, Thorlacius H. Actin-related protein 2/3 complex regulates neutrophil extracellular trap expulsion and lung damage in abdominal sepsis. Am J Physiol Lung Cell Mol Physiol 2022; 322:L662-L672. [PMID: 35272488 DOI: 10.1152/ajplung.00318.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Neutrophil extracellular trap (NET) formation is a key feature in sepsis. The aim of the present study was to examine the role of the actin cytoskeleton in regulating the expulsion of NETs. Actin-related protein 2/3 (Arp 2/3) complex is an important regulator of F-actin polymerization. Co-incubation with CK666, a specific Arp 2/3 inhibitor, decreased PMA-induced NET formation in vitro. CK666 not only abolished F-actin polymerization but also caused intracellular retention of NETs. Inhibition of Arp 2/3 reduced NET formation on circulating neutrophils and in the bronchoalveolar space in mice undergoing cecal ligation and puncture (CLP). Notably, treatment with CK666 attenuated CLP-induced neutrophil recruitment, edema formation and tissue damage in the lungs. Moreover, Arp 2/3 inhibition decreased levels of CXCL-1 and interleukin-6 in the lung and plasma of septic animals. Taken together, this study shows that expulsion of NETs is regulated by the actin cytoskeleton and that inhibition of Arp 2/3-dependent F-actin polymerization not only decrease NET formation but also protect against pathological inflammation and tissue damage in septic lung injury. Thus, we suggest that targeting NET release is a novel and useful way to ameliorate lung damage in abdominal sepsis.
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Affiliation(s)
- Zhiyi Ding
- Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden
| | - Feifei Du
- Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden
| | - Carl-Fredrik Rönnow
- Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden
| | - Yongzhi Wang
- Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden
| | - Milladur Rahman
- Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden
| | - Henrik Thorlacius
- Department of Clinical Sciences, Section for Surgery, Lund University, Malmö, Sweden
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31
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Cubillo-Martínez AA, Pereyra MA, Garfias Y, Guluarte C, Zenteno E, Sánchez-Salgado JL. Extracellular traps involved in invertebrate immune mechanisms. FISH & SHELLFISH IMMUNOLOGY 2022; 121:380-386. [PMID: 35045319 DOI: 10.1016/j.fsi.2022.01.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/11/2022] [Accepted: 01/15/2022] [Indexed: 06/14/2023]
Abstract
The invertebrate immune system possesses a mechanism named extracellular traps (ETs), it has been identified that this mechanism immobilizes and kills pathogens. ETs formation induces modification of histones, chromatin decondensation, and mixes with granule molecules, releasing them into the extracellular space as a defense mechanism. In the present review, we provide an overview on the identification of triggering stimuli such as pathogens, PAMPs, DAMPs, and chemical stimuli, discuss the participation of potential signaling pathways involving MAPK, PI3K, PKC, and ERK molecules that lead to NADPH oxidase or mitochondrial ROS production, and explore the potential relationship with several proteins such as myeloperoxidase, heat sock proteins, peroxinectin, elastase, and apolipoproteins. Furthermore, we also discuss the association of ETs with other immune mechanisms that could collaborate in the elimination of pathogens.
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Affiliation(s)
| | - Mohamed Alí Pereyra
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, CP 04510, Mexico City, Mexico
| | - Yonathan Garfias
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, CP 04510, Mexico City, Mexico; Research Unit, Instituto de Oftalmología "Conde de Valenciana IAP", CP 06800, Mexico City, Mexico
| | - Crystal Guluarte
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, CP 04510, Mexico City, Mexico
| | - Edgar Zenteno
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, CP 04510, Mexico City, Mexico.
| | - José Luis Sánchez-Salgado
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, CP 04510, Mexico City, Mexico.
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32
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Huang C, Du J, Ji B, Gong S, Geng C, Miao Y, Shen Q, Gu W, Wang L, Meng Q. The Eriocheir sinensis calcium/calmodulin-dependent protein kinase II activates apoptosis to resist Spiroplasma eriocheiris infection. FISH & SHELLFISH IMMUNOLOGY 2022; 121:223-231. [PMID: 34986398 DOI: 10.1016/j.fsi.2021.12.054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/21/2021] [Accepted: 12/29/2021] [Indexed: 06/14/2023]
Abstract
Calcium/calmodulin-dependent protein kinase II is a downstream mediator of calcium signalling and participates in the regulation of various cellular physiological functions. In previous studies, the expression of Eriocheir sinensis CaMKII (EsCaMKII) was significantly decreased in the thoracic ganglion after Spiroplasma eriocheiris infection, as shown using TMT-based quantitative proteomic analysis; however, the specific functions of EsCaMKII are still unclear. In this study, the full-length cDNA of EsCaMKII was 3314 bp long, consisting of a 1605 bp open reading frame encoding a protein of 535 amino acids, including a 258 aa serine/threonine protein kinase catalytic domain (EsCaMKII-CD). EsCaMKII is highly transcribed in haemocytes, nerves (thoracic ganglion), gills, and muscles, but lowly transcribed in the hepatopancreas, heart, and intestines. The transcription levels of EsCaMKII were altered in E. sinensis haemocytes after S. eriocheiris infection. After the over-expression of EsCaMKII-CD in RAW264.7 cells, the apoptosis rate of RAW264.7 cells was significantly increased. After the over-expression of EsCaMKII-CD, the morphology of RAW264.7 cells became worse after being infected with S. eriocheiris. Meanwhile, the copy number of S. eriocheiris in RAW264.7 cells was significantly decreased. From 48 h to 96 h after EsCaMKII RNA interference, the transcription levels of EsCaMKII decreased significantly. The transcription of apoptosis genes and cell apoptosis were also inhibited in haemocytes after EsCaMKII RNAi. The knockdown of EsCaMKII by RNAi resulted in significant increases in the copy number of S. eriocheiris and in the mortality of crabs during S. eriocheiris infection. These results indicate that EsCaMKII could promote the apoptosis of E. sinensis and enhance its ability to resist S. eriocheiris infection.
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Affiliation(s)
- Chen Huang
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Jie Du
- Animal Husbandry and Veterinary College, Jiangsu Vocational College of Agriculture and Forestry, Jurong, Jiangsu 212400, China
| | - Bairu Ji
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Sinan Gong
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Chao Geng
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Yanyang Miao
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Qingchun Shen
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Wei Gu
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China
| | - Li Wang
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, China.
| | - Qingguo Meng
- Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Marine Science and Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing 210023, China.
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Wolach O, Martinod K. Casting a NET on cancer: the multiple roles for neutrophil extracellular traps in cancer. Curr Opin Hematol 2022; 29:53-62. [PMID: 34854835 DOI: 10.1097/moh.0000000000000690] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW The role of the innate immune system has become widely appreciated in cancer and cancer-associated disorders. Neutrophils, the most abundant circulating leukocytes, have prognostic value in determining cancer progression and survival. One of the ways by which neutrophils negatively impact outcome is by formation of neutrophil extracellular traps (NETs) which result in release of nuclear chromatin and bioactive proteins into the extracellular space. Here, we review the evidence for NETs contributions to cancer progression, metastasis, and cancer-associated thrombosis (CAT). RECENT FINDINGS NETs are increased across several cancer types and predict progression and adverse outcome. Several preclinical and clinical observations implicate NETs in promoting tumor growth, angiogenesis and metastasis via distinct pathways. Furthermore, NETs are shown to contribute to resistance to immunotherapy. NETs also emerge as key players in the prothrombotic phenotype associated with cancer that can result in potentially life-threatening arterial and venous thrombosis. Recent mechanistic insights expose several potential targets to inhibit NET formation and disrupt the interaction between NETs and tumor cells. SUMMARY Clinical and translational insights highlight the central role of NETs in cancer progression and metastasis, disease resistance and CAT. Targeting NETs and NET-associated pathways may represent a novel approach to treat cancer.
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Affiliation(s)
- Ofir Wolach
- Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Kimberly Martinod
- Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
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Álvarez de Haro N, Van AP, Robb CT, Rossi AG, Desbois AP. Release of chromatin extracellular traps by phagocytes of Atlantic salmon, Salmo salar (Linnaeus, 1758). FISH & SHELLFISH IMMUNOLOGY 2021; 119:209-219. [PMID: 34438058 PMCID: PMC8653909 DOI: 10.1016/j.fsi.2021.08.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/18/2021] [Accepted: 08/22/2021] [Indexed: 05/05/2023]
Abstract
Neutrophils release chromatin extracellular traps (ETs) as part of the fish innate immune response to counter the threats posed by microbial pathogens. However, relatively little attention has been paid to this phenomenon in many commercially farmed species, despite the importance of understanding host-pathogen interactions and the potential to influence ET release to reduce disease outbreaks. The aim of this present study was to investigate the release of ETs by Atlantic salmon (Salmo salar L.) immune cells. Extracellular structures resembling ETs of different morphology were observed by fluorescence microscopy in neutrophil suspensions in vitro, as these structures stained positively with Sytox Green and were digestible with DNase I. Immunofluorescence studies confirmed the ET structures to be decorated with histones H1 and H2A and neutrophil elastase, which are characteristic for ETs in mammals and other organisms. Although the ETs were released spontaneously, release in neutrophil suspensions was stimulated most significantly with 5 μg/ml calcium ionophore (CaI) for 1 h, whilst the fish pathogenic bacterium Aeromonas salmonicida (isolates 30411 and Hooke) also exerted a stimulatory effect. Microscopic observations revealed bacteria in association with ETs, and fewer bacterial colonies of A. salmonicida Hooke were recovered at 3 h after co-incubation with neutrophils that had been induced to release ETs. Interestingly, spontaneous release of ETs was inversely associated with fish mass (p < 0.05), a surrogate for age. Moreover, suspensions enriched for macrophages and stimulated with 5 μg/ml CaI released ET-like structures that occasionally led to the formation of large clumps of cells. A deeper understanding for the roles and functions of ETs within innate immunity of fish hosts, and their interaction with microbial pathogens, may open new avenues towards protecting cultured stocks against infectious diseases.
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Affiliation(s)
- Neila Álvarez de Haro
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, FK9 4LA, United Kingdom
| | - Andre P Van
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, FK9 4LA, United Kingdom
| | - Calum T Robb
- University of Edinburgh, Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom
| | - Adriano G Rossi
- University of Edinburgh, Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom
| | - Andrew P Desbois
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, FK9 4LA, United Kingdom.
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Aguilar-Díaz H, Quiroz-Castañeda RE, Salazar-Morales K, Cossío-Bayúgar R, Miranda-Miranda E. Tick Immunobiology and Extracellular Traps: An Integrative Vision to Control of Vectors. Pathogens 2021; 10:pathogens10111511. [PMID: 34832666 PMCID: PMC8621429 DOI: 10.3390/pathogens10111511] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/01/2021] [Accepted: 11/16/2021] [Indexed: 01/21/2023] Open
Abstract
Ticks are hematophagous ectoparasites that infest a diverse number of vertebrate hosts. The tick immunobiology plays a significant role in establishing and transmitting many pathogens to their hosts. To control tick infestations, the acaricide application is a commonly used method with severe environmental consequences and the selection of tick-resistant populations. With these drawbacks, new tick control methods need to be developed, and the immune system of ticks contains a plethora of potential candidates for vaccine design. Additionally, tick immunity is based on an orchestrated action of humoral and cellular immune responses. Therefore, the actors of these responses are the object of our study in this review since they are new targets in anti-tick vaccine design. We present their role in the immune response that positions them as feasible targets that can be blocked, inhibited, interfered with, and overexpressed, and then elucidate a new method to control tick infestations through the development of vaccines. We also propose Extracellular Traps Formation (ETosis) in ticks as a process to eliminate their natural enemies and those pathogens they transmit (vectorial capacity), which results attractive since they are a source of acting molecules with potential use as vaccines.
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Affiliation(s)
- Hugo Aguilar-Díaz
- Unidad de Artropodología, Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad INIFAP, Jiutepec 62574, Mexico; (R.C.-B.); (E.M.-M.)
- Correspondence:
| | - Rosa Estela Quiroz-Castañeda
- Unidad de Anaplasmosis, Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad INIFAP, Jiutepec 62574, Mexico;
| | - Karina Salazar-Morales
- Centro de Investigaciones Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico;
| | - Raquel Cossío-Bayúgar
- Unidad de Artropodología, Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad INIFAP, Jiutepec 62574, Mexico; (R.C.-B.); (E.M.-M.)
| | - Estefan Miranda-Miranda
- Unidad de Artropodología, Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad INIFAP, Jiutepec 62574, Mexico; (R.C.-B.); (E.M.-M.)
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Chen RY, Keddie BA. Galleria mellonella (Lepidoptera: Pyralidae) Hemocytes Release Extracellular Traps That Confer Protection Against Bacterial Infection in the Hemocoel. JOURNAL OF INSECT SCIENCE (ONLINE) 2021; 21:6449199. [PMID: 34865034 PMCID: PMC8643984 DOI: 10.1093/jisesa/ieab092] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Indexed: 05/06/2023]
Abstract
Extracellular traps (ETs) released from vertebrate and invertebrate immune cells consist of chromatin and toxic granule contents that are capable of immobilizing and killing microbes. This recently described innate immune response is not well documented in insects. The present study found that ETs were released by hemocytes of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae) in vivo and ex vivo after bacterial stimulation. ET release (ETosis), hemolymph coagulation, and melanization likely contributed to the immobilization and killing of the bacteria. The injection of G. mellonella hemocyte deoxyribonucleic acid (DNA) in the presence of bacteria increased bacterial clearance rate and prolonged insect survival. Taken together, these results indicate the presence of insect hemocyte extracellular traps (IHETs) that protect the insect against microbial infection in the hemocoel and represent the first documentation of ETs in insects in vivo.
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Affiliation(s)
- Robin Y Chen
- Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada
- Corresponding author, e-mail:
| | - B Andrew Keddie
- Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada
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Han Y, Zhang Q, Chen L, Yang D, Zhao J. Mitochondria are essential for antibacterial extracellular trap formation mediated by zymosan in hemocytes of Ruditapes philippinarum. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2021; 121:104094. [PMID: 33823212 DOI: 10.1016/j.dci.2021.104094] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 03/29/2021] [Accepted: 03/29/2021] [Indexed: 06/12/2023]
Abstract
The formation of extracellular traps (ETs) is an important innate immune mechanism that serves to combat different invading pathogens. In this study, zymosan significantly induced the formation of ETs in the hemocytes of Ruditapes philippinarum, and this effect was accompanied by translocation of the mitochondria to the cell surface. Zymosan stimulation clearly induced an increase in intracellular ROS and MPO production and an overexpression of ROS-related genes (PI3K, AKT and HIF). In response to the ROS burst, the mitochondrial membrane potential decreased, and the mitochondrial permeability transition pore opened. Conversely, mitochondrial superoxide inhibitor (Mito-TEMPO) significantly inhibited the formation of ETs, suggesting that mitochondrial ROS were necessary for the formation of ETs. In addition, we found that zymosan-induced ETs showed antibacterial activities against gram-negative and gram-positive bacteria, such as Vibrio anguillarum, Vibrio harveyi, Escherichia coli and Micrococcus luteus. Taken together, these findings elucidated a new antibacterial approach for R. philippinarum and highlighted the role of mitochondria in the formation of zymosan-induced ETs.
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Affiliation(s)
- Yijing Han
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Qianqian Zhang
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China
| | - Lizhu Chen
- Shandong Marine Resource and Environment Research Institute, Yantai, Shandong, 264006, PR China
| | - Dinglong Yang
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China.
| | - Jianmin Zhao
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Center for Ocean Mega-science, Chinese Academy of Sciences, Qingdao, Shandong, 266071, PR China.
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Bouallegui Y. A Comprehensive Review on Crustaceans' Immune System With a Focus on Freshwater Crayfish in Relation to Crayfish Plague Disease. Front Immunol 2021; 12:667787. [PMID: 34054837 PMCID: PMC8155518 DOI: 10.3389/fimmu.2021.667787] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/27/2021] [Indexed: 12/21/2022] Open
Abstract
Freshwater crayfish immunity has received great attention due to the need for urgent conservation. This concern has increased the understanding of the cellular and humoral defense systems, although the regulatory mechanisms involved in these processes need updating. There are, however, aspects of the immune response that require clarification and integration. The particular issues addressed in this review include an overall description of the oomycete Aphanomyces astaci, the causative agent of the pandemic plague disease, which affects freshwater crayfish, and an overview of crustaceans' immunity with a focus on freshwater crayfish. It includes a classification system of hemocyte sub-types, the molecular factors involved in hematopoiesis and the differential role of the hemocyte subpopulations in cell-mediated responses, including hemocyte infiltration, inflammation, encapsulation and the link with the extracellular trap cell death pathway (ETosis). In addition, other topics discussed include the identity and functions of hyaline cells, the generation of neoplasia, and the emerging topic of the role of sessile hemocytes in peripheral immunity. Finally, attention is paid to the molecular execution of the immune response, from recognition by the pattern recognition receptors (PRRs), the role of the signaling network in propagating and maintaining the immune signals, to the effector elements such as the putative function of the Down syndrome adhesion molecules (Dscam) in innate immune memory.
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Affiliation(s)
- Younes Bouallegui
- LR01ES14 Laboratory of Environmental Biomonitoring, Faculty of Sciences of Bizerte, University of Carthage, Bizerte, Tunisia
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39
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Fukuchi M, Kamide Y, Ueki S, Miyabe Y, Konno Y, Oka N, Takeuchi H, Koyota S, Hirokawa M, Yamada T, Melo RCN, Weller PF, Taniguchi M. Eosinophil ETosis-Mediated Release of Galectin-10 in Eosinophilic Granulomatosis With Polyangiitis. Arthritis Rheumatol 2021; 73:1683-1693. [PMID: 33750029 DOI: 10.1002/art.41727] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 03/04/2021] [Indexed: 01/02/2023]
Abstract
OBJECTIVE Eosinophils are tissue-dwelling immune cells. Accumulating evidence indicates that a type of cell death termed ETosis is an important cell fate involved in the pathophysiology of inflammatory diseases. Although the critical role of eosinophils in eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) is well established, the presence of eosinophil ETosis (EETosis) is poorly understood. We undertook this study to better understand the characteristics of EETosis. METHODS In vitro studies using blood-derived eosinophils were conducted to characterize EETosis. The occurrence of EETosis in tissues from patients with EGPA was studied by immunostaining and electron microscopy. Serum concentrations of eosinophil-derived proteins in healthy controls, patients with asthma, and EGPA patients with active disease or with disease in remission (n = 15 per group) were examined. RESULTS EETosis was reliant on reactive oxygen species and peptidylarginine deiminase type 4-dependent histone citrullination, resulting in the cytolytic release of net-like eosinophil extracellular traps, free galectin-10, and membrane-bound intact granules. The signature of EETosis, including loss of cytoplasmic galectin-10 and deposition of granules, was observed in eosinophils infiltrating various tissues from EGPA patients. Serum eosinophil granule proteins and galectin-10 levels were increased in EGPA and positively correlated with disease activity as assessed by the Birmingham Vasculitis Activity Score (r = 0.8531, P < 0.0001 for galectin-10). When normalized to blood eosinophil counts, this correlation remained for galectin-10 (r = 0.7168, P < 0.0001) but not for granule proteins. Galectin-10 levels in active EGPA positively correlated with serum interleukin-5 levels. CONCLUSION Eosinophils infiltrating diseased tissues in EGPA undergo EETosis. Considering the exclusive expression and large pool of cytoplasmic galectin-10 in eosinophils, elevated serum galectin-10 levels in patients with EGPA might reflect the systemic occurrence of cytolytic EETosis.
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Affiliation(s)
| | | | | | | | | | - Nobuyuki Oka
- Kyoto Konoe Rehabilitation Hospital, Kyoto, Japan
| | | | | | | | | | - Rossana C N Melo
- Federal University of Juiz de Fora, Juiz de Fora, Brazil, and Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States
| | - Peter F Weller
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States
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Piscirickettsia salmonis-Triggered Extracellular Traps Formation as an Innate Immune Response of Atlantic Salmon-Derived Polymorphonuclear Neutrophils. BIOLOGY 2021; 10:biology10030206. [PMID: 33803375 PMCID: PMC7999065 DOI: 10.3390/biology10030206] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 12/21/2022]
Abstract
Simple Summary Within innate immunity, polymorphonuclear neutrophils (PMN) are the most abundant leukocyte population. Alongside PMN, monocytes, eosinophils, and basophils are also known to exist. All of them can release extracellular traps (ETs), a complex web-like structure composed of chromatin decorated with nuclear histones, granular enzymes, peptides, and proteins, to firmly entrap invasive pathogens, thereby slowing dissemination and helping to develop proper immune responses against bacteria, fungi, viruses, and parasites. Here, we showed for the first time that Atlantic salmon-derived PMN released ETs-like structures in vitro, in response to highly pathogenic facultative intracellular rickettsial bacteria Piscirickettsia salmonis. The release of ET-like structures from PMN could be a new alternative to improve farmed salmon’s defense against pathogens. Abstract Extracellular traps (ETs) are webs of DNA, citrullinated histones, anti-microbial peptides, and proteins that were not previously reported in Atlantic salmon (Salmo salar). ETs are mainly released from polymorphonuclear neutrophils (PMN) and are considered a novel PMN-derived effector mechanism against different invasive pathogens. Here, we showed that Atlantic salmon-derived PMN released ETs-like structures in vitro in response to highly pathogenic facultative intracellular rickettsial bacteria Piscirickettsia salmonis. PMN were isolated from pre-smolt Atlantic salmon and stimulated in vitro with oleic acid and P. salmonis. Extracellular DNA was measured using the PicoGreen™ dye, while immunofluorescence image analysis was used to confirm the classical components of salmonid-extruded ETs. Future studies are required to better understand the role of Atlantic salmon-derived ETs orchestrating innate/adaptive immunity and the knowledge on regulation pathways involved in this cell death process. Thus, comprehension of salmonid-derived ETs against P. salmonis might represent novel alternative strategies to improve host innate defense mechanisms of farmed salmon against closely related rickettsial bacteria, as a complement to disease prevention and control strategies.
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Drury B, Hardisty G, Gray RD, Ho GT. Neutrophil Extracellular Traps in Inflammatory Bowel Disease: Pathogenic Mechanisms and Clinical Translation. Cell Mol Gastroenterol Hepatol 2021; 12:321-333. [PMID: 33689803 PMCID: PMC8166923 DOI: 10.1016/j.jcmgh.2021.03.002] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 03/01/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023]
Abstract
The Inflammatory Bowel Diseases (IBD), Ulcerative Colitis (UC) and Crohn's Disease (CD) are characterised by chronic non-resolving gut mucosal inflammation involving innate and adaptive immune responses. Neutrophils, usually regarded as first responders in inflammation, are a key presence in the gut mucosal inflammatory milieu in IBD. Here, we review the role of neutrophil extracellular trap (NET) formation as a potential effector disease mechanism. NETs are extracellular webs of chromatin, microbicidal proteins and oxidative enzymes that are released by neutrophils to contain pathogens. NETs contribute to the pathogenesis of several immune-mediated diseases such as systemic lupus erythematosus and rheumatoid arthritis; and recently, as a major tissue damaging process involved in the host response to severe acute respiratory syndrome coronavirus 2 infection. NETs are pertinent as a defence mechanism at the gut mucosal interphase exposed to high levels of bacteria, viruses and fungi. On the other hand, NETs can also potentiate and perpetuate gut inflammation. In this review, we discuss the broad protective vs. pathogenic roles of NETs, explanatory factors that could lead to an increase in NET formation in IBD and how NETs may contribute to gut inflammation and IBD-related complications. Finally, we summarise therapeutic opportunities to target NETs in IBD.
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Affiliation(s)
- Broc Drury
- Centre for Inflammation Research, University of Edinburgh, Scotland, United Kingdom
| | - Gareth Hardisty
- Centre for Inflammation Research, University of Edinburgh, Scotland, United Kingdom
| | - Robert D Gray
- Centre for Inflammation Research, University of Edinburgh, Scotland, United Kingdom
| | - Gwo-Tzer Ho
- Centre for Inflammation Research, University of Edinburgh, Scotland, United Kingdom.
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Han Y, Chen L, Zhang Q, Yu D, Yang D, Zhao J. Hemocyte extracellular traps of Manila clam Ruditapes philippinarum: Production characteristics and antibacterial effects. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2021; 116:103953. [PMID: 33275994 DOI: 10.1016/j.dci.2020.103953] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 11/27/2020] [Accepted: 11/28/2020] [Indexed: 06/12/2023]
Abstract
Extracellular traps (ETs) have been found to be an important strategy of mammals to immobilize and kill invading microorganisms. In the present study, we observed the formation of ETs in the hemocytes of marine mollusks Ruditapes philippinarum in response to challenge from bacteria Vibrio anguillarum, and examined the potential factors and signaling pathways underling this process. We detected an increase of reactive oxygen species (ROS) and myeloperoxidase (MPO) production during ETosis, accompanied by significantly up-regulated expression of ROS-related and MPO genes. The suppression of ETs structures by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenyleneiodonium chloride, DPI) and MPO inhibitor (aminobenzoic acid hydrazide, ABAH) further confirmed the essential roles ROS and MPO played in ETosis. Furthermore, ET production could be inhibited by phosphotidylinsitol-3-kinase (PI3K) inhibitor (LY294002) and extracellular regulated protein kinase (ERK) inhibitor (U0126), suggesting the idea that both the PI3K and ERK pathways were suggested to function during ETosis. In addition, the ETosis process was accompanied by enhancement of glycolysis-related enzymatic activities, e.g., pyruvate kinase (PK) and hexokinase (HK), and over-expression of the glycolysis-related genes, e.g., PK, HK and glucose transport protein (GLUT), indicating high involvement of glycolysis in the ETosis process. Furthermore, our scanning electron microscopy (SEM) observation and antibacterial activities test successfully showed the patterns how clam ETs entrapped and killed the invading V. anguillarum. Taken together, our results revealed that ETosis with bactericidal effect increased ROS, MPO and glycolysis level and carried out in a ROS-, MPO-, PI3K-ERK-dependent manner.
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Affiliation(s)
- Yijing Han
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Center for Ocean Mega-science, Chinese Academy of Sciences, Qingdao, Shandong, 266071, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Lizhu Chen
- Shandong Marine Resource and Environment Research Institute, Yantai, 264006, PR China
| | - Qianqian Zhang
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Center for Ocean Mega-science, Chinese Academy of Sciences, Qingdao, Shandong, 266071, PR China
| | - Daode Yu
- Marine Biology Institute of Shandong Province, Qingdao, Shandong, 266002, PR China
| | - Dinglong Yang
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Center for Ocean Mega-science, Chinese Academy of Sciences, Qingdao, Shandong, 266071, PR China.
| | - Jianmin Zhao
- Muping Coastal Environment Research Station, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, PR China; Center for Ocean Mega-science, Chinese Academy of Sciences, Qingdao, Shandong, 266071, PR China.
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Ramos-Martínez E, Hernández-González L, Ramos-Martínez I, Pérez-Campos Mayoral L, López-Cortés GI, Pérez-Campos E, Mayoral Andrade G, Hernández-Huerta MT, José MV. Multiple Origins of Extracellular DNA Traps. Front Immunol 2021; 12:621311. [PMID: 33717121 PMCID: PMC7943724 DOI: 10.3389/fimmu.2021.621311] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 01/06/2021] [Indexed: 01/21/2023] Open
Abstract
Extracellular DNA traps (ETs) are evolutionarily conserved antimicrobial mechanisms present in protozoa, plants, and animals. In this review, we compare their similarities in species of different taxa, and put forward the hypothesis that ETs have multiple origins. Our results are consistent with a process of evolutionary convergence in multicellular organisms through the application of a congruency test. Furthermore, we discuss why multicellularity is related to the presence of a mechanism initiating the formation of ETs.
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Affiliation(s)
- Edgar Ramos-Martínez
- School of Sciences, Benito Juárez Autonomous University of Oaxaca, Oaxaca, Mexico
| | | | - Iván Ramos-Martínez
- Glycobiology, Cell Growth and Tissue Repair Research Unit (Gly-CRRET), Université Paris Est Créteil (UPEC), Créteil, France
| | - Laura Pérez-Campos Mayoral
- Research Centre Medicine UNAM-UABJO, Faculty of Medicine, Benito Juárez Autonomous University of Oaxaca, Oaxaca, Mexico
| | | | - Eduardo Pérez-Campos
- Biochemistry and Immunology Unit, National Technological of Mexico/ITOaxaca, Oaxaca, Mexico
- Research Centre Medicine UNAM-UABJO, Faculty of Medicine, Benito Juárez Autonomous University of Oaxaca, Oaxaca, Mexico
| | - Gabriel Mayoral Andrade
- Research Centre Medicine UNAM-UABJO, Faculty of Medicine, Benito Juárez Autonomous University of Oaxaca, Oaxaca, Mexico
| | | | - Marco V. José
- Theoretical Biology Group, National Autonomous University of Mexico, Mexico City, Mexico
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Rios MR, Garoffolo G, Rinaldi G, Megia-Fernandez A, Ferrari S, Robb CT, Rossi AG, Pesce M, Bradley M. A fluorogenic peptide-based smartprobe for the detection of neutrophil extracellular traps and inflammation. Chem Commun (Camb) 2021; 57:97-100. [DOI: 10.1039/d0cc07028a] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A highly specific, fluorogenic probe detects human neutrophil elastase (hNE) in activated neutrophils and Neutrophil Extracellular Traps (NETs).
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Affiliation(s)
- Maria R. Rios
- EaStCHEM School of Chemistry
- University of Edinburgh
- EH9 3FJ Edinburgh
- UK
| | - Gloria Garoffolo
- Tissue Engineering Research Unit
- Centro Cardiologico Monzino
- IRCCS
- Milan
- Italy
| | - Giulia Rinaldi
- Centre for Inflammation Research
- Queen's Medical Research Institute
- University of Edinburgh
- UK
| | | | - Silvia Ferrari
- Tissue Engineering Research Unit
- Centro Cardiologico Monzino
- IRCCS
- Milan
- Italy
| | - Calum T. Robb
- Centre for Inflammation Research
- Queen's Medical Research Institute
- University of Edinburgh
- UK
| | - Adriano G. Rossi
- Centre for Inflammation Research
- Queen's Medical Research Institute
- University of Edinburgh
- UK
| | - Maurizio Pesce
- Tissue Engineering Research Unit
- Centro Cardiologico Monzino
- IRCCS
- Milan
- Italy
| | - Mark Bradley
- EaStCHEM School of Chemistry
- University of Edinburgh
- EH9 3FJ Edinburgh
- UK
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45
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Lu XJ, Deng Q, Thompson KD. Editorial: The Function of Phagocytes in Non-Mammals. Front Immunol 2020; 11:628847. [PMID: 33362804 PMCID: PMC7759483 DOI: 10.3389/fimmu.2020.628847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 11/20/2020] [Indexed: 11/13/2022] Open
Affiliation(s)
- Xin-Jiang Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China.,Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, China.,Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, China.,Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China
| | - Qing Deng
- Department of Biological Sciences, Purdue University, West Lafayette, IN, United States
| | - Kim Dawn Thompson
- Aquaculture Research Group, Moredun Research Institute, Penicuik, United Kingdom
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46
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Robb CT, Goepp M, Rossi AG, Yao C. Non-steroidal anti-inflammatory drugs, prostaglandins, and COVID-19. Br J Pharmacol 2020; 177:4899-4920. [PMID: 32700336 PMCID: PMC7405053 DOI: 10.1111/bph.15206] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/09/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
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Affiliation(s)
- Calum T. Robb
- Centre for Inflammation Research, Queen's Medical Research InstituteThe University of EdinburghEdinburghUK
| | - Marie Goepp
- Centre for Inflammation Research, Queen's Medical Research InstituteThe University of EdinburghEdinburghUK
| | - Adriano G. Rossi
- Centre for Inflammation Research, Queen's Medical Research InstituteThe University of EdinburghEdinburghUK
| | - Chengcan Yao
- Centre for Inflammation Research, Queen's Medical Research InstituteThe University of EdinburghEdinburghUK
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47
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Parisi MG, Parrinello D, Stabili L, Cammarata M. Cnidarian Immunity and the Repertoire of Defense Mechanisms in Anthozoans. BIOLOGY 2020; 9:E283. [PMID: 32932829 PMCID: PMC7563517 DOI: 10.3390/biology9090283] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/04/2020] [Accepted: 09/04/2020] [Indexed: 02/07/2023]
Abstract
Anthozoa is the most specious class of the phylum Cnidaria that is phylogenetically basal within the Metazoa. It is an interesting group for studying the evolution of mutualisms and immunity, for despite their morphological simplicity, Anthozoans are unexpectedly immunologically complex, with large genomes and gene families similar to those of the Bilateria. Evidence indicates that the Anthozoan innate immune system is not only involved in the disruption of harmful microorganisms, but is also crucial in structuring tissue-associated microbial communities that are essential components of the cnidarian holobiont and useful to the animal's health for several functions including metabolism, immune defense, development, and behavior. Here, we report on the current state of the art of Anthozoan immunity. Like other invertebrates, Anthozoans possess immune mechanisms based on self/non-self-recognition. Although lacking adaptive immunity, they use a diverse repertoire of immune receptor signaling pathways (PRRs) to recognize a broad array of conserved microorganism-associated molecular patterns (MAMP). The intracellular signaling cascades lead to gene transcription up to endpoints of release of molecules that kill the pathogens, defend the self by maintaining homeostasis, and modulate the wound repair process. The cells play a fundamental role in immunity, as they display phagocytic activities and secrete mucus, which acts as a physicochemical barrier preventing or slowing down the proliferation of potential invaders. Finally, we describe the current state of knowledge of some immune effectors in Anthozoan species, including the potential role of toxins and the inflammatory response in the Mediterranean Anthozoan Anemonia viridis following injection of various foreign particles differing in type and dimensions, including pathogenetic bacteria.
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Affiliation(s)
- Maria Giovanna Parisi
- Department of Earth and Marine Sciences, University of Palermo, 90128 Palermo, Italy;
| | - Daniela Parrinello
- Department of Earth and Marine Sciences, University of Palermo, 90128 Palermo, Italy;
| | - Loredana Stabili
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy;
| | - Matteo Cammarata
- Department of Earth and Marine Sciences, University of Palermo, 90128 Palermo, Italy;
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Sezer N, Kılıç Ö, Sıkdokur E, Çayır A, Belivermiş M. Impacts of elevated pCO 2 on Mediterranean mussel (Mytilus galloprovincialis): Metal bioaccumulation, physiological and cellular parameters. MARINE ENVIRONMENTAL RESEARCH 2020; 160:104987. [PMID: 32907725 DOI: 10.1016/j.marenvres.2020.104987] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/06/2020] [Accepted: 04/09/2020] [Indexed: 06/11/2023]
Abstract
Ocean acidification alters physiology, acid-base balance and metabolic activity in marine animals. Near future elevated pCO2 conditions could be expected to influence the bioaccumulation of metals, feeding rate and immune parameters in marine mussels. To better understand such impairments, a series of laboratory-controlled experiment was conducted by using a model marine mussel, Mytilus galloprovincialis. The mussels were exposed to three pH conditions according to the projected CO2 emissions in the near future (one ambient: 8.10 and two reduced: 7.80 and 7.50). At first, the bioconcentration of Ag and Cd was studied in both juvenile (2.5 cm) and adult (5.1 cm) mussels by using a highly sensitive radiotracer method (110mAg and 109Cd). The uptake and depuration kinetics were followed 21 and 30 days, respectively. The biokinetic experiments demonstrated that the effect of ocean acidification on bioconcentration was metal-specific and size-specific. The uptake, depuration and tissue distribution of 110mAg were not affected by elevated pCO2 in both juvenile and adult mussels, whereas 109Cd uptake significantly increased with decreasing pH in juveniles but not in adults. Regardless of pH, 110mAg accumulated more efficiently in juvenile mussels than adult mussels. After executing the biokinetic experiment, the perturbation was sustained by using the same mussels and the same experimental set-up, which enabled us to determine filtration rate, haemocyte viability, lysosomal membrane stability, circulating cell-free nucleic acids (ccf-NAs) and protein (ccf-protein) levels. The filtration rate and haemocyte viability gradually decreased by increasing pCO2 level, whereas the lysosomal membrane stability, ccf-NAs, and ccf-protein levels remained unchanged in the mussels exposed to elevated pCO2 for eighty-two days. This study suggests that acidified seawater partially shift metal bioaccumulation, physiological and cellular parameters in the mussel Mytilus galloprovincialis.
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Affiliation(s)
- Narin Sezer
- Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Turkey
| | - Önder Kılıç
- Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Turkey
| | - Ercan Sıkdokur
- Institute of Graduate Studies in Sciences, Istanbul University, Suleymaniye, Istanbul, Turkey
| | - Akın Çayır
- Vocational Health College, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
| | - Murat Belivermiş
- Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Turkey.
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Auguste M, Balbi T, Ciacci C, Canesi L. Conservation of Cell Communication Systems in Invertebrate Host-Defence Mechanisms: Possible Role in Immunity and Disease. BIOLOGY 2020; 9:E234. [PMID: 32824821 PMCID: PMC7464772 DOI: 10.3390/biology9080234] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/16/2020] [Accepted: 08/17/2020] [Indexed: 12/14/2022]
Abstract
Innate immunity is continuously revealing multiple and highly conserved host-defence mechanisms. Studies on mammalian immunocytes are showing different communication systems that may play a role in coordinating innate immune responses also in invertebrates. Extracellular traps (ETs) are an immune response by which cells release net-like material, including DNA, histones and proteins. ETs are thought to immobilise and kill microorganisms, but are also involved in inflammation and autoimmune disease. Immune cells are also known to communicate through extracellular vesicles secreted in the extracellular environment or exosomes, which can carry a variety of different signalling molecules. Tunnelling nanotubes (TNTs) represent a direct cell-to-cell communication over a long distance, that allow for bi- or uni-directional transfer of cellular components between cells. Their functional role in a number of physio-pathological processes, including immune responses and pathogen transfer, has been underlined. Although ETs, exosomes, and TNTs have been described in invertebrate species, their possible role in immune responses is not fully understood. In this work, available data on these communication systems are summarised, in an attempt to provide basic information for further studies on their relevance in invertebrate immunity and disease.
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Affiliation(s)
- Manon Auguste
- Department of Earth Environment and Life Sciences (DISTAV), University of Genoa, 16136 Genoa, Italy; (M.A.); (T.B.)
| | - Teresa Balbi
- Department of Earth Environment and Life Sciences (DISTAV), University of Genoa, 16136 Genoa, Italy; (M.A.); (T.B.)
| | - Caterina Ciacci
- Department of Biomolecular Sciences (DIBS), University “Carlo Bo” of Urbino, 61029 Urbino, Italy;
| | - Laura Canesi
- Department of Earth Environment and Life Sciences (DISTAV), University of Genoa, 16136 Genoa, Italy; (M.A.); (T.B.)
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50
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Coste Grahl MV, Perin APA, Lopes FC, Porto BN, Uberti AF, Canavoso LE, Stanisçuaski F, Fruttero LL. The role of extracellular nucleic acids in the immune system modulation of Rhodnius prolixus (Hemiptera: Reduviidae). PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 2020; 167:104591. [PMID: 32527424 DOI: 10.1016/j.pestbp.2020.104591] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 04/11/2020] [Accepted: 04/20/2020] [Indexed: 06/11/2023]
Abstract
Extracellular traps (ETs) are extracellular nucleic acids associated with cytoplasmic proteins that may aid in the capture and killing of pathogens. To date, only a few insects were shown to display this kind of immune response. Jaburetox, a peptide derived from jack bean urease, showed toxic effects in Rhodnius prolixus, affecting its immune response. The present study aims to evaluate the role of extracellular nucleic acids in R. prolixus' immune response, using Jaburetox as a model entomotoxin. The insects were treated with extracellular nucleic acids and/or Jaburetox, and the cellular and humoral responses were assessed. We also evaluated the release of extracellular nucleic acids induced by toxins, and performed immunocompetence assays using pathogenic bacteria. Our results demonstrated that extracellular nucleic acids can modulate the insect immune responses, either alone or associated with the toxin. Although RNA and DNA induced a cellular immune response, only DNA was able to neutralize the Jaburetox-induced aggregation of hemocytes. Likewise, the activation of the humoral response was different for RNA and DNA. Nevertheless, it was observed that both, extracellular DNA and RNA, immunocompensated the Jaburetox effects on insect defenses upon the challenge of a pathogenic bacterium. The toxin was not able to alter cellular viability, in spite of inducing an increase in the reactive species of oxygen formation. In conclusion, we have demonstrated a protective role for extracellular nucleic acids in R. prolixus´ immune response to toxins and pathogenic bacteria.
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Affiliation(s)
- Matheus V Coste Grahl
- Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Building 43431, CEP 91501-970 Porto Alegre, RS, Brazil.
| | - Ana Paula A Perin
- Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Building 43431, CEP 91501-970 Porto Alegre, RS, Brazil.
| | - Fernanda C Lopes
- Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Building 43431, CEP 91501-970 Porto Alegre, RS, Brazil.
| | - Bárbara N Porto
- Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6690, Building 60, CEP 90610-000 Porto Alegre, Brazil.
| | - Augusto F Uberti
- Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul, Pontifícia Universidade Católica do Rio Grande do Sul, CEP 90610-000 Porto Alegre, Brazil.
| | - Lilian E Canavoso
- Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
| | - Fernanda Stanisçuaski
- Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Building 43431, CEP 91501-970 Porto Alegre, RS, Brazil; Department of Molecular Biology and Biotechnology, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Building 43431, CEP 91501-970 Porto Alegre, RS, Brazil.
| | - Leonardo L Fruttero
- Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
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