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Iaquinto G, Aufiero VR, Mazzarella G, Lucariello A, Panico L, Melina R, Iaquinto S, De Luca A, Sellitto C. Pathogens in Crohn's Disease: The Role of Adherent Invasive Escherichia coli. Crit Rev Eukaryot Gene Expr 2024; 34:83-99. [PMID: 38305291 DOI: 10.1615/critreveukaryotgeneexpr.2023050088] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
In Crohn's disease (CD), gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia coli strain was isolated in the ileal mucosa of CD patients. This strain, called adherent invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within macrophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.
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Affiliation(s)
- Gaetano Iaquinto
- Gastroenterology Division, S. Rita Hospital, Atripalda, Avellino, Italy
| | - Vera Rotondi Aufiero
- Institute of Food Sciences, CNR, Avellino, Italy and Department of Translational Medical Science and E.L.F.I.D, University "Federico II" Napoli, Italy
| | - Giuseppe Mazzarella
- Institute of Food Sciences, CNR, Avellino, Italy and Department of Translational Medical Science and E.L.F.I.D, University "Federico II" Napoli, Italy
| | - Angela Lucariello
- Department of Sport Sciences and Wellness, University of Naples "Parthenope," 80100, Naples, Italy
| | - Luigi Panico
- Pathological Anatomy and Histology Unit, Monaldi Hospital, Napoli, Italy
| | - Raffaele Melina
- Department of Gastroenterology, San G. Moscati Hospital, Avellino, Italy
| | | | - Antonio De Luca
- Department of Mental Health and Physics, Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy
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2
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Montero DA, Vidal RM, Velasco J, George S, Lucero Y, Gómez LA, Carreño LJ, García-Betancourt R, O’Ryan M. Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development. Front Med (Lausanne) 2023; 10:1155751. [PMID: 37215733 PMCID: PMC10196187 DOI: 10.3389/fmed.2023.1155751] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/14/2023] [Indexed: 05/24/2023] Open
Abstract
Vibrio cholerae is the causative agent of cholera, a highly contagious diarrheal disease affecting millions worldwide each year. Cholera is a major public health problem, primarily in countries with poor sanitary conditions and regions affected by natural disasters, where access to safe drinking water is limited. In this narrative review, we aim to summarize the current understanding of the evolution of virulence and pathogenesis of V. cholerae as well as provide an overview of the immune response against this pathogen. We highlight that V. cholerae has a remarkable ability to adapt and evolve, which is a global concern because it increases the risk of cholera outbreaks and the spread of the disease to new regions, making its control even more challenging. Furthermore, we show that this pathogen expresses several virulence factors enabling it to efficiently colonize the human intestine and cause cholera. A cumulative body of work also shows that V. cholerae infection triggers an inflammatory response that influences the development of immune memory against cholera. Lastly, we reviewed the status of licensed cholera vaccines, those undergoing clinical evaluation, and recent progress in developing next-generation vaccines. This review offers a comprehensive view of V. cholerae and identifies knowledge gaps that must be addressed to develop more effective cholera vaccines.
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Affiliation(s)
- David A. Montero
- Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | - Roberto M. Vidal
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Instituto Milenio de Inmunología e Inmunoterapia, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Juliana Velasco
- Unidad de Paciente Crítico, Clínica Hospital del Profesor, Santiago, Chile
- Programa de Formación de Especialista en Medicina de Urgencia, Universidad Andrés Bello, Santiago, Chile
| | - Sergio George
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Yalda Lucero
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Departamento de Pediatría y Cirugía Infantil, Hospital Dr. Roberto del Rio, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Leonardo A. Gómez
- Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
| | - Leandro J. Carreño
- Instituto Milenio de Inmunología e Inmunoterapia, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Richard García-Betancourt
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Miguel O’Ryan
- Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
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Abstract
PURPOSE OF REVIEW The vermiform cecal appendix is a small thin pouch-like tube of intestinal tissue situated in the lower right abdomen. It is attached at the junction of the large intestine between the ascending colon and small intestine. Historically, the appendix has been labeled redundant with no significant function, a remnant of evolution. This idea was thought to represent a function that may have been critical for survival that became nonsignificant over time. Evolutionary biologists deemed it to be a vestigial organ that early in human evolution was a dedicated organ that was useful and exploited by herbivorous ancestors. RECENT FINDINGS Currently, the vermiform cecal appendix has generated significant renewed research interest. As such it has been reported to present a site with a high concentration of lymphoid tissue and a biofilm microbiome that approximately mirrors that which is found in the large bowel. SUMMARY Research suggests that the vermiform cecal appendix may be the site of a safe-house biofilm that could re-inoculate the large bowel. Given that the appendix has no known role in digestion, the network of lymphoid tissue and microbiome could constitute an initial site of bacterial translocations that can influence early life ontology and immunological tolerance. A dysbiotic microbiome in the appendix is posited to trigger inflammatory sequelae.
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Magold AI, Swartz MA. Pathogenic Exploitation of Lymphatic Vessels. Cells 2022; 11:979. [PMID: 35326430 PMCID: PMC8946894 DOI: 10.3390/cells11060979] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 03/07/2022] [Accepted: 03/09/2022] [Indexed: 02/06/2023] Open
Abstract
Lymphatic vessels provide a critical line of communication between peripheral tissues and their draining lymph nodes, which is necessary for robust immune responses against infectious agents. At the same time, lymphatics help shape the nature and kinetics of immune responses to ensure resolution, limit tissue damage, and prevent autoimmune responses. A variety of pathogens have developed strategies to exploit these functions, from multicellular organisms like nematodes to bacteria, viruses, and prions. While lymphatic vessels serve as transport routes for the dissemination of many pathogens, their hypoxic and immune-suppressive environments can provide survival niches for others. Lymphatics can be exploited as perineural niches, for inter-organ distribution among highly motile carrier cells, as effective replicative niches, and as alternative routes in response to therapy. Recent studies have broadened our understanding of lymphatic involvement in pathogenic spread to include a wider range of pathogens, as well as new mechanisms of exploitation, which we summarize here.
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Affiliation(s)
- Alexandra I. Magold
- Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA;
| | - Melody A. Swartz
- Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA;
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA
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5
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Delon L, Gibson R, Prestidge C, Thierry B. Mechanisms of uptake and transport of particulate formulations in the small intestine. J Control Release 2022; 343:584-599. [PMID: 35149142 DOI: 10.1016/j.jconrel.2022.02.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 10/19/2022]
Abstract
Micro- and nano-scale particulate formulations are widely investigated towards improving the oral bioavailability of both biologics and drugs with low solubility and/or low intestinal permeability. Particulate formulations harnessing physiological intestinal transport pathways have recently yielded remarkably high oral bioavailabilities, illustrating the need for better understanding the specific pathways underpinning particle small intestinal absorption and the relative role of intestinal cells. Mechanistic knowledge has been hampered by the well acknowledged limitations of current in vitro, in vivo and ex vivo models relevant to the human intestinal physiology and the lack of standardization in studies reporting absorption data. Here we review the relevant literature and critically discusses absorption pathways with a focus on the role of specific intestinal epithelial and immune cells. We conclude that while Microfold (M) cells are a valid target for oral vaccines, enterocytes play a greater role in the systemic bioavailability of orally administrated particulate formulations, particularly within the sub-micron size range. We also comment on less-reported mechanisms such as paracellular permeability of particles, persorption due to cell damage and uptake by migratory immune cells.
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Affiliation(s)
- Ludivine Delon
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, Adelaide, South Australia 5095, Australia; Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
| | - Rachel Gibson
- Australia School of Allied Health Science and Practice, University of Adelaide, South Australia 5005, Australia
| | - Clive Prestidge
- Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
| | - Benjamin Thierry
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, Adelaide, South Australia 5095, Australia.
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6
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Physical properties of lactic acid bacteria influence the level of protection against influenza infection in mice. PLoS One 2021; 16:e0251784. [PMID: 34003877 PMCID: PMC8130949 DOI: 10.1371/journal.pone.0251784] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 05/03/2021] [Indexed: 11/20/2022] Open
Abstract
We evaluated whether the water dispersibility of lactic acid bacteria (Enterococcus faecalis KH2) affects their efficacy. When cultured lactic acid bacteria are washed, heat-killed, and powdered, adhesion occurs between results in aggregation (non-treated lactic acid bacteria, n-LAB). However, dispersed lactic acid bacteria (d-LAB) with a lower number of aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. Mice were administered n-LAB or d-LAB Peyer’s patches in the small intestine were observed. Following n-LAB administration, a high amount of aggregated bacteria drifting in the intestinal mucosa was observed; meanwhile, d-LAB reached the Peyer’s patches and was absorbed into them. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in the influenza yield of bronchoalveolar lavage fluids on day 3 post-infection and neutralizing antibody titers of sera and influenza virus-specific immunoglobulin A in the feces on day 14 post-infection. Therefore, the physical properties of lactic acid bacteria affect their efficacy; controlling their water dispersibility can improve their effectiveness.
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7
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Cho JY, Liu R, Macbeth JC, Hsiao A. The Interface of Vibrio cholerae and the Gut Microbiome. Gut Microbes 2021; 13:1937015. [PMID: 34180341 PMCID: PMC8244777 DOI: 10.1080/19490976.2021.1937015] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/18/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023] Open
Abstract
The bacterium Vibrio cholerae is the etiologic agent of the severe human diarrheal disease cholera. The gut microbiome, or the native community of microorganisms found in the human gastrointestinal tract, is increasingly being recognized as a factor in driving susceptibility to infection, in vivo fitness, and host interactions of this pathogen. Here, we review a subset of the emerging studies in how gut microbiome structure and microbial function are able to drive V. cholerae virulence gene regulation, metabolism, and modulate host immune responses to cholera infection and vaccination. Improved mechanistic understanding of commensal-pathogen interactions offers new perspectives in the design of prophylactic and therapeutic approaches for cholera control.
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Affiliation(s)
- Jennifer Y. Cho
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
- Department of Biochemistry, University of California, Riverside, California, USA
| | - Rui Liu
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
- Graduate Program in Genetics, Genomics, and Bioinformatics, University of California, Riverside, California, USA
| | - John C. Macbeth
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, California, USA
| | - Ansel Hsiao
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
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8
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Moule MG, Cirillo JD. Mycobacterium tuberculosis Dissemination Plays a Critical Role in Pathogenesis. Front Cell Infect Microbiol 2020; 10:65. [PMID: 32161724 PMCID: PMC7053427 DOI: 10.3389/fcimb.2020.00065] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 02/07/2020] [Indexed: 12/27/2022] Open
Abstract
Mycobacterium tuberculosis is primarily a respiratory pathogen. However, 15% of infections worldwide occur at extrapulmonary sites causing additional complications for diagnosis and treatment of the disease. In addition, dissemination of M. tuberculosis out of the lungs is thought to be more than just a rare event leading to extrapulmonary tuberculosis, but rather a prerequisite step that occurs during all infections, producing secondary lesions that can become latent or productive. In this review we will cover the clinical range of extrapulmonary infections and the process of dissemination including evidence from both historical medical literature and animal experiments for dissemination and subsequent reseeding of the lungs through the lymphatic and circulatory systems. While the mechanisms of M. tuberculosis dissemination are not fully understood, we will discuss the various models that have been proposed to address how this process may occur and summarize the bacterial virulence factors that facilitate M. tuberculosis dissemination.
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Affiliation(s)
- Madeleine G. Moule
- Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX, United States
| | - Jeffrey D. Cirillo
- Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX, United States
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9
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Murugaiah C, Nik Mohd Noor NZ, Al-Talib H, Mustafa S, Manickam R, Pattabhiraman L. Immunohistochemical, histological and ultrastructural evaluation of protection provided by cholera vaccine against V. cholerae O139. Microb Pathog 2020; 140:103964. [PMID: 31904450 DOI: 10.1016/j.micpath.2020.103964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 01/01/2020] [Accepted: 01/01/2020] [Indexed: 11/30/2022]
Abstract
In our previous study, complete protection was observed in rabbit immunized with 1 × 1010 CFU of live attenuated VCUSM21P vaccine against challenge with 1 × 109 CFU Vibrio cholerae O139. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological, immunohistochemical and ultrastructural techniques. Severe pathology is evident in wild type injected ileum in non-immunized, showing extensive villous destruction, edema, necrosis and inflammation with infiltration of large numbers of inflammatory cells, extensive damage to the villi and microvilli with pore formation. Histology of ileum injected with wild type in immunized rabbit shows no significant pathological changes except for a few inflammatory cells in lamina propria with mild edema in mucosa and submucosa. immunohistochemical staining revealed O139 antigens of wild type are seen in the lamina propria of edematous villi, muscularis mucosa and submucosa with weak presence in the muscle coat in non-immunized rabbit after challenged with wild type in non-immunized rabbits, but in immunized rabbit localisation of the O139 LPS antigen is seen at the tips of the intact villi, within lamina propria and muscularis mucosa only. These observations suggest that the vaccine can effectively protect animals from any pathologic changes and eliminate V. cholerae O139 from the immunized animals.
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Affiliation(s)
- Chandrika Murugaiah
- Department of Biomedical Sciences and Therapeutics, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, 88400, Kota Kinabalu, Sabah, Malaysia; School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia.
| | - Nik Zuraina Nik Mohd Noor
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia
| | - Hassanain Al-Talib
- Laboratory Medical Science Cluster, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh, 47000, Selangor, Malaysia
| | - Shyamoli Mustafa
- Pathology Unit, Faculty of Medicine, AIMST University, 08100, Bedong, Kedah, Malaysia
| | - Ravichandran Manickam
- Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Semeling, 08100, Bedong, Kedah, Malaysia
| | - Lalitha Pattabhiraman
- Faculty of Medical Sciences, AIMST University, Semeling, 08100, Bedong, Kedah, Malaysia
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10
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Shaikh H, Lynch J, Kim J, Excler JL. Current and future cholera vaccines. Vaccine 2019; 38 Suppl 1:A118-A126. [PMID: 31879125 DOI: 10.1016/j.vaccine.2019.12.011] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 11/08/2019] [Accepted: 12/06/2019] [Indexed: 01/21/2023]
Abstract
Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has been recommended as an additional public health tool along with WASH in cholera endemic countries and in areas at risk for outbreaks. The new generation OCV is safe and offers good protection in older children and adults while limited protection in younger children less than five years of age has been observed. The combination of direct vaccine protection and vaccine herd immunity effects makes OCV highly cost-effective and, therefore, attractive for use in developing countries. Additionally, in recent studies OCV was safe in pregnant women, supporting its use in pregnant women in cholera endemic countries. However, knowledge need to be developed for current vaccines for their prolonged duration of protection and vaccines need improvements for better immune response in younger children. A single dose vaccination regimen would be more cost-effective and easier to deliver. Recent approaches have focused on designing genetically attenuated cholera strains for use in single-dose cholera vaccines. The global demand for OCV has been boosted by the WHO recommendation to use OCV and is driven largely by epidemics and outbreaks and has been increasing due to the availability of cheaper easy-to-use vaccines, feasibility of mass OCV vaccination campaigns, demonstration of protection to underserved population in precarious situations, and vaccine costs being borne by Gavi (Vaccine Alliance). For rapid access in emergency and equitable distribution of OCV in cholera-endemic low-income countries, a global OCV stockpile was established in 2013 with support from the Global Alliance for Vaccines and Immunization. The three WHO-prequalified vaccines are Dukoral®, Shanchol™, Euvichol® (and Euvichol® Plus presentation), the latter two being included in the stockpile.
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Affiliation(s)
- Hanif Shaikh
- International Vaccine Institute, Seoul, Republic of Korea; K.E.M. Hospital Research Centre, Pune, Maharashtra, India.
| | - Julia Lynch
- International Vaccine Institute, Seoul, Republic of Korea
| | - Jerome Kim
- International Vaccine Institute, Seoul, Republic of Korea
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11
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Evaluating Shigella flexneri Pathogenesis in the Human Enteroid Model. Infect Immun 2019; 87:IAI.00740-18. [PMID: 30642900 PMCID: PMC6434113 DOI: 10.1128/iai.00740-18] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 01/06/2019] [Indexed: 01/02/2023] Open
Abstract
The enteric pathogen Shigella is one of the leading causes of moderate-to-severe diarrhea and death in young children in developing countries. Transformed cell lines and animal models have been widely used to study Shigella pathogenesis. The enteric pathogen Shigella is one of the leading causes of moderate-to-severe diarrhea and death in young children in developing countries. Transformed cell lines and animal models have been widely used to study Shigella pathogenesis. In addition to altered physiology, transformed cell lines are composed of a single cell type that does not sufficiently represent the complex multicellular environment of the human colon. Most available animal models do not accurately mimic human disease. The human intestinal enteroid model, derived from LGR5+ stem cell-containing intestinal crypts from healthy subjects, represents a technological leap in human gastrointestinal system modeling and provides a more physiologically relevant system that includes multiple cell types and features of the human intestine. We established the utility of this model for studying basic aspects of Shigella pathogenesis and host responses. In this study, we show that Shigellaflexneri is capable of infecting and replicating intracellularly in human enteroids derived from different segments of the intestine. Apical invasion by S. flexneri is very limited but increases ∼10-fold when enteroids are differentiated to include M cells. Invasion via the basolateral surface was at least 2-log10 units more efficient than apical infection. Increased secretion of interleukin-8 and higher expression levels of the mucin glycoprotein Muc2 were observed in the enteroids following S. flexneri infection. The human enteroid model promises to bridge some of the gaps between traditional cell culture, animal models, and human infection.
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12
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Klisuric A, Thierry B, Delon L, Prestidge CA, Gibson RJ. Identifying human and murine M cells in vitro. Exp Biol Med (Maywood) 2019; 244:554-564. [PMID: 30907132 DOI: 10.1177/1535370219838674] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
IMPACT STATEMENT The study of M cells, a specialized epithelial cell type found in the follicle-associated epithelium, is hampered by the lack of a universal M cell marker. As such, many studies lack reliable and universally recognized methods to identify M cells in their proposed models. As a result of this it is difficult to ascertain whether the effects observed are due to the presence of M cells or an unaccounted variable. The outcome of this review is the thorough evaluation of the many M cell markers that have been used in the literature thus far and a proposed criterion for the identification of M cells for future publications. This will hopefully lead to an improvement in the quality of future publications in this field.
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Affiliation(s)
- Ana Klisuric
- 1 Division of Health Sciences, University of South Australia, Adelaide 5000, Australia.,2 ARC Centre of Excellence in Convergent Bio and Nano Science and Technology, University of South Australia, Frome Road, Adelaide 5000, Australia.,3 School of Pharmacy and Medical Science, University of South Australia, Adelaide 5000, Australia
| | - Benjamin Thierry
- 2 ARC Centre of Excellence in Convergent Bio and Nano Science and Technology, University of South Australia, Frome Road, Adelaide 5000, Australia.,4 Future Industries Institute, University of South Australia, Mawson Lakes 5095, Australia
| | - Ludivine Delon
- 1 Division of Health Sciences, University of South Australia, Adelaide 5000, Australia.,2 ARC Centre of Excellence in Convergent Bio and Nano Science and Technology, University of South Australia, Frome Road, Adelaide 5000, Australia.,4 Future Industries Institute, University of South Australia, Mawson Lakes 5095, Australia
| | - Clive A Prestidge
- 1 Division of Health Sciences, University of South Australia, Adelaide 5000, Australia.,2 ARC Centre of Excellence in Convergent Bio and Nano Science and Technology, University of South Australia, Frome Road, Adelaide 5000, Australia
| | - Rachel J Gibson
- 1 Division of Health Sciences, University of South Australia, Adelaide 5000, Australia
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13
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Yang JS, An SJ, Jang MS, Song M, Han SH. IgM specific to lipopolysaccharide of Vibrio cholerae is a surrogate antibody isotype responsible for serum vibriocidal activity. PLoS One 2019; 14:e0213507. [PMID: 30845262 PMCID: PMC6405115 DOI: 10.1371/journal.pone.0213507] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Accepted: 02/24/2019] [Indexed: 12/21/2022] Open
Abstract
Serum vibriocidal antibody assays have long been used to evaluate the immunogenicity of cholera vaccines formulated with killed whole-cell Vibrio cholerae. However, the antibody isotypes responsible for the serum vibriocidal activity are not fully characterized. In this study, we examined 20 clinical serum samples obtained from human subjects who had been vaccinated with a killed, whole-cell cholera vaccine and a positive control, human convalescent sera with high vibriocidal activity, to determine which isotype antibody is associated with the vibriocidal activity. Antibody isotypes from pooled convalescent sera were fractionated by size-exclusion column chromatography, and the major vibriocidal activity was detected in the IgM fraction. Depletion of IgM antibodies in the convalescent sera produced a significant (P<0.05) decrease in vibriocidal activity (16-fold decrease), whereas only a small change was observed with depletion of IgG or IgA. In addition, anti-LPS IgM antibody showed the highest correlation with vibriocidal activity (Spearman correlation coefficient r = 0.846) among antibody isotypes against heat-killed V. cholerae, lipopolysaccharide (LPS), or major outer membrane protein (Omp U), while total IgG, IgA, or IgM antibody level was not correlated with vibriocidal activity in the 20 human clinical serum samples. Furthermore, human convalescent sera significantly (P<0.001) inhibited the attachment of V. cholerae to HT-29, a human intestinal epithelial cell in vitro. Interestingly, IgM-depleted convalescent sera could not effectively inhibit bacterial adherence compared with non-depleted sera (P<0.05). Finally, bacterial adhesion was significantly inhibited by sera with high vibriocidal titer compared with low-titer sera (P = 0.014). Collectively, we demonstrated that anti-V. cholerae LPS IgM is highly correlated with serum vibriocidal activity and it could be a surrogate antibody isotype representing protective antibodies against V. cholerae.
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Affiliation(s)
- Jae Seung Yang
- Clinical Research Laboratory, International Vaccine Institute, Seoul, Republic of Korea
| | - So Jung An
- Vaccine Process Development, International Vaccine Institute, Seoul, Republic of Korea
| | - Mi Seon Jang
- Clinical Research Laboratory, International Vaccine Institute, Seoul, Republic of Korea
| | - Manki Song
- Clinical Research Laboratory, International Vaccine Institute, Seoul, Republic of Korea
| | - Seung Hyun Han
- Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
- * E-mail:
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14
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The vermiform appendix: an immunological organ sustaining a microbiome inoculum. Clin Sci (Lond) 2019; 133:1-8. [PMID: 30606811 DOI: 10.1042/cs20180956] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 11/29/2018] [Accepted: 12/04/2018] [Indexed: 12/12/2022]
Abstract
The hominoid vermiform appendix has been characterized as a diverticulum of the caecum and describes an entity at the juxtaposition of the colon in the confluence of tanias. The independent development of the lymphoid follicle centres of the appendix is progressed at birth in the presence of the intestinal commensal microbiome, an obligatory prompt for the diversification of intestinal and extra-intestinal mucosal immunological tissue. In the vermiform appendix, this activity is centred on further developing the inventory of primary antibodies and the maturation of T- and B-lymphocyte cells in the follicles within the lymphoid tissue. Furthermore, the columnar epithelia, enterocytes and goblet cells comprise the complement of cells that occupy the lamina propria and muscularis mucosae of the vermiform appendix's mucosa, while macrophages and an abundance of immunoglobulin A and immunoglobulin G generating plasma cells seed the lamina propria Intraepithelial immune cells consisting predominantly of specific CD8+ T regulatory lymphocytes occupy sites in the appendix analogous to those present in the intestinal epithelia of the caecal colon. The complement of bacterial genera concealed in the vermiform appendix is posited extant as a biofilm inoculum of the intestinal commensal microbiome. This facilitates re-inoculation of the proximal colon and to a lesser degree the terminal ilium post an intestinal perturbation such as occurs with daily lifestyle stressors, dietary choices and the short-term administration of antibiotics rather than an infectious fulminant colitis. A plausible appreciation results of the importance of multiple immunological aspects of a healthy vermiform appendix and the provision of a commensal biofilm to the gut that repairs a dysbiotic microbiome contributing to balancing intestinal pro- and anti-inflammatory activity for maintaining homeostasis in the gut. Since the composition of the gut microbiome can vary over the short-term and long-term, it is plausible that the appendix inoculum may be instrumental in maintaining the intestinal microbiome.
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Lin SF, Jiang PL, Tsai JS, Huang YY, Lin SY, Lin JH, Liu DZ. Surface assembly of poly(I:C) on polyethyleneimine-modified gelatin nanoparticles as immunostimulatory carriers for mucosal antigen delivery. J Biomed Mater Res B Appl Biomater 2018; 107:1228-1237. [PMID: 30339742 DOI: 10.1002/jbm.b.34215] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 06/19/2018] [Accepted: 07/21/2018] [Indexed: 12/13/2022]
Abstract
The mucosal immune system is the host's first line of defense against invasion by foreign pathogens. Gelatin nanoparticles (GNPs) are suitable carriers for the delivery of antigens via various routes of administration. In the present study, GNPs were modified with polyethyleneimine (PEI), a positively charged polymer. Then, ovalbumin (OVA) and polyinosinic:polycytidylic acid (poly(I:C)), an immunostimulant, were adsorbed onto the surface of the positively charged GNPs. We assessed whether GNPs could act as an effective mucosal vaccine that is capable of inducing both mucosal and systemic immune responses. The results showed that GNPs effectively adsorbed OVA/poly(I:C), facilitated cellular uptake by RAW 264.7 macrophage cells and murine bone marrow-derived dendritic cells (BMDCs) in vitro, and led to increased expression of the maturation markers CD80 and CD86 on BMDCs. Furthermore, GNPs induced increased secretion of proinflammatory cytokines in both RAW 264.7 and BMDCs. C57BL/6 mice that were intranasally twice-immunized with OVA/poly(I:C)-loaded GNPs produced high levels of serum OVA-specific IgG antibodies and secretory IgA in nasal and lung lavage. Spleen cells from immunized mice were collected and re-stimulated with OVA, and results showed significantly augmented production of IFN-γ, IL-4, IL-5, and IL-6 in mice that received OVA/poly(I:C)-loaded GNPs. Moreover, intranasal immunization with OVA/poly(I:C)-loaded GNPs resulted in the inhibition of EG7 tumor growth in C57BL/6 mice. Taken together, these results indicate that nasal administration of OVA/poly(I:C)-loaded GNPs elicited effective mucosal and systemic immune responses, which might be useful for further applications of antigen delivery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1228-1237, 2019.
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Affiliation(s)
- Shen-Fu Lin
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, 250, Wu-Hsing Street, Taipei, 110, Taiwan, ROC
| | - Ping-Lun Jiang
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, 250, Wu-Hsing Street, Taipei, 110, Taiwan, ROC.,Office of Research and Development, Providence University, 200, Sec. 7, Taiwan Boulevard, Taichung City, 433, Taiwan, ROC
| | - Jeng-Shiang Tsai
- Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, 1, Section 1, Jen-Ai Road, Taipei, 100, Taiwan, ROC
| | - Yi-You Huang
- Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, 1, Section 1, Jen-Ai Road, Taipei, 100, Taiwan, ROC
| | - Shyr-Yi Lin
- Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan, ROC
| | - Jiunn-Horng Lin
- Animal Technology Laboratories, Agricultural Technology Research Institute, No. 1, Ln. 51, Dahu Rd., Hsinchu City, Taiwan, ROC
| | - Der-Zen Liu
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, 250, Wu-Hsing Street, Taipei, 110, Taiwan, ROC
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16
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Stojanovska V, McQuade RM, Fraser S, Prakash M, Gondalia S, Stavely R, Palombo E, Apostolopoulos V, Sakkal S, Nurgali K. Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. PLoS One 2018; 13:e0198359. [PMID: 29894476 PMCID: PMC5997344 DOI: 10.1371/journal.pone.0198359] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 05/17/2018] [Indexed: 02/07/2023] Open
Abstract
Oxaliplatin is a platinum-based chemotherapeutic used for cancer treatment. Its use associates with peripheral neuropathies and chronic gastrointestinal side-effects. Oxaliplatin induces immunogenic cell death by provoking the presentation of damage associated molecular patterns. The damage associated molecular patterns high-mobility group box 1 (HMGB1) protein exerts pro-inflammatory cytokine-like activity and binds to toll-like receptors (namely TLR4). Gastrointestinal microbiota may influence chemotherapeutic efficacy and contribute to local and systemic inflammation. We studied effects of oxaliplatin treatment on 1) TLR4 and high-mobility group box 1 expression within the colon; 2) gastrointestinal microbiota composition; 3) inflammation within the colon; 4) changes in Peyer's patches and mesenteric lymph nodes immune populations in mice. TLR4+ cells displayed pseudopodia-like extensions characteristic of antigen sampling co-localised with high-mobility group box 1 -overexpressing cells in the colonic lamina propria from oxaliplatin-treated animals. Oxaliplatin treatment caused significant reduction in Parabacteroides and Prevotella1, but increase in Prevotella2 and Odoribacter bacteria at the genus level. Downregulation of pro-inflammatory cytokines and chemokines in colon samples, a reduction in macrophages and dendritic cells in mesenteric lymph nodes were found after oxaliplatin treatment. In conclusion, oxaliplatin treatment caused morphological changes in TLR4+ cells, increase in gram-negative microbiota and enhanced HMGB1 expression associated with immunosuppression in the colon.
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Affiliation(s)
- Vanesa Stojanovska
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Rachel M. McQuade
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Sarah Fraser
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Monica Prakash
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Shakuntla Gondalia
- Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Melbourne, Victoria, Australia
| | - Rhian Stavely
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Enzo Palombo
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Hawthorn, Melbourne, Victoria, Australia
| | - Vasso Apostolopoulos
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Samy Sakkal
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Kulmira Nurgali
- College of Health and Biomedicine, Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
- Department of Medicine Western Health, The University of Melbourne, Regenerative Medicine and Stem Cells Program, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne, Victoria, Australia
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17
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Some news from the unknown soldier, the Peyer's patch macrophage. Cell Immunol 2018; 330:159-167. [PMID: 29395860 DOI: 10.1016/j.cellimm.2018.01.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 01/15/2018] [Accepted: 01/16/2018] [Indexed: 12/24/2022]
Abstract
In mammals, macrophages (MF) are present in virtually all tissues where they serve many different functions linked primarily to the maintenance of homeostasis, innate defense against pathogens, tissue repair and metabolism. Although some of these functions appear common to all tissues, others are specific to the homing tissue. Thus, MF become adapted to perform particular functions in a given tissue. Accordingly, MF express common markers but also sets of tissue-specific markers linked to dedicated functions. One of the largest pool of MF in the body lines up the wall of the gut. Located in the small intestine, Peyer's patches (PP) are primary antigen sampling and mucosal immune response inductive sites. Surprisingly, although markers of intestinal MF, such as F4/80, have been identified more than 30 years ago, MF of PP escaped any kind of phenotypic description and remained "unknown" for decades. In absence of MF identification, the characterization of the PP mononuclear phagocyte system (MPS) functions has been impaired. However, taking into account that PP are privileged sites of entry for pathogens, it is important to understand how the latter are handled by and/or escape the PP MPS, especially MF, which role in killing invaders is well known. This review focuses on recent advances on the PP MPS, which have allowed, through new criteria of PP phagocyte subset identification, the characterization of PP MF origin, diversity, specificity, location and functions.
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Klećkowska-Nawrot JE, Goździewska-Harłajczuk K, Łupicki D, Marycz K, Nawara T, Barszcz K, Kowalczyk A, Rosenberger J, Łukaszewicz E. The differences in the eyelids microstructure and the conjunctiva-associated lymphoid tissue between selected ornamental and wild birds as a result of adaptation to their habitat. ACTA ZOOL-STOCKHOLM 2017. [DOI: 10.1111/azo.12223] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Joanna E. Klećkowska-Nawrot
- Department of Animal Physiology and Biostructure; Faculty of Veterinary Medicine; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Karolina Goździewska-Harłajczuk
- Department of Animal Physiology and Biostructure; Faculty of Veterinary Medicine; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Dariusz Łupicki
- Museum of Natural History of the Faculty of Biology and Animal Science; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Krzysztof Marycz
- Electron Microscopy Laboratory; Faculty of Biology and Animal Science; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Tomasz Nawara
- Electron Microscopy Laboratory; Faculty of Biology and Animal Science; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Karolina Barszcz
- Department of Morphological Sciences; Faculty of Veterinary Medicine; Warsaw University of Life Sciences; Warsaw Poland
| | - Artur Kowalczyk
- Division of Poultry Breeding; Faculty of Biology and Animal Science; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Joanna Rosenberger
- Division of Poultry Breeding; Faculty of Biology and Animal Science; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
| | - Ewa Łukaszewicz
- Division of Poultry Breeding; Faculty of Biology and Animal Science; Wroclaw University of Environmental and Life Sciences; Wroclaw Poland
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19
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Da Silva C, Wagner C, Bonnardel J, Gorvel JP, Lelouard H. The Peyer's Patch Mononuclear Phagocyte System at Steady State and during Infection. Front Immunol 2017; 8:1254. [PMID: 29038658 PMCID: PMC5630697 DOI: 10.3389/fimmu.2017.01254] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 09/20/2017] [Indexed: 12/14/2022] Open
Abstract
The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer’s patches (PPs) are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is, therefore, critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches. Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome (SED) remains less well understood. Nevertheless, it is clear that the mononuclear phagocyte system (MPS) plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the SED, interact with M cells, and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP mononuclear phagocyte subsets. It gives an overview of their diversity, specificity, location, and functions. Interaction of PP phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP phagocyte identification. Finally, known alterations affecting the different phagocyte subsets during PP stimulation or infection are discussed.
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Affiliation(s)
| | - Camille Wagner
- Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France
| | - Johnny Bonnardel
- Laboratory of Myeloid Cell Ontogeny and Functional Specialisation, VIB Inflammation Research Center, Ghent, Belgium
| | | | - Hugues Lelouard
- Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France
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20
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Ishisono K, Yabe T, Kitaguchi K. Citrus pectin attenuates endotoxin shock via suppression of Toll-like receptor signaling in Peyer's patch myeloid cells. J Nutr Biochem 2017; 50:38-45. [PMID: 29031241 DOI: 10.1016/j.jnutbio.2017.07.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 07/06/2017] [Accepted: 07/25/2017] [Indexed: 12/14/2022]
Abstract
Pectin, a water-soluble dietary fiber, has been found to improve survival in endotoxin shock. However, the underlying mechanism by which pectin exerts its protective effect against endotoxin shock remains unknown. Apart from its prebiotic effects, it has been suggested that pectin directly affects immune cells to regulate inflammatory responses. In this study, we investigated the direct effect of pectin in murine model of endotoxin shock. Citrus pectin solution was administered to male C57BL/6 mice for 10 days. Thereafter, hypothermia was induced in the mice with intraperitoneal injection of lipopolysaccharide (LPS). The pectin-treated mice showed attenuation of both the decrease in rectal temperature and increase in serum IL-6 level as compared to vehicle control mice. Simultaneously, the pectin-treated mice showed reduced levels of inflammatory cytokine mRNA in Peyer's patches and mesenteric lymph nodes, but not in the spleen. Peyer's patch cells from the pectin-treated mice were sorted and their levels of IL-6 production on LPS stimulation were measured. The results of ex vivo analysis indicated that IL-6 secretion from CD11c+ cells was suppressed by oral administration of pectin. Furthermore, IL-6 secretion from Toll-like receptor (TLR)-activated RAW264.7 cells was suppressed by pretreatment with pectin in vitro. This suppression was observed even with degraded pectin pretreatment but not with polygalacturonic acid, as the principal constituent of the pectin backbone. Taken together, these results suggest that pectin intake suppresses TLR-induced inflammatory cytokine expression in Peyer's patch myeloid cells, presumably through inhibition of TLR signaling by the pectin side chains.
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Affiliation(s)
- Keita Ishisono
- United Graduate School of Agricultural Science, Gifu University, Gifu, Japan
| | - Tomio Yabe
- United Graduate School of Agricultural Science, Gifu University, Gifu, Japan; Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan; Center for Highly Advanced Integration of Nano and Life Sciences, Gifu University (G-CHAIN), Gifu, Japan
| | - Kohji Kitaguchi
- United Graduate School of Agricultural Science, Gifu University, Gifu, Japan; Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.
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21
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Evaluation of intestinal damage caused by V. cholerae O139, an in vivo study. Microb Pathog 2017; 105:25-29. [DOI: 10.1016/j.micpath.2017.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 02/02/2017] [Accepted: 02/03/2017] [Indexed: 11/21/2022]
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22
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Shawki A, McCole DF. Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli. Cell Mol Gastroenterol Hepatol 2017; 3:41-50. [PMID: 28174756 PMCID: PMC5247418 DOI: 10.1016/j.jcmgh.2016.10.004] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 10/14/2016] [Indexed: 12/12/2022]
Abstract
Pathobiont expansion, such as that of adherent-invasive Escherichia coli (AIEC), is an emerging factor associated with inflammatory bowel disease. The intestinal epithelial barrier is the first line of defense against these pathogens. Inflammation plays a critical role in altering the epithelial barrier and is a major factor involved in promoting the expansion and pathogenesis of AIEC. AIEC in turn can exacerbate intestinal epithelial barrier dysfunction by targeting multiple elements of the barrier. One critical element of the epithelial barrier is the tight junction. Increasing evidence suggests that AIEC may selectively target protein components of tight junctions, leading to increased barrier permeability. This may represent one mechanism by which AIEC could contribute to the development of inflammatory bowel disease. This review article discusses potential mechanisms by which AIEC can disrupt epithelial tight junction function and intestinal barrier function.
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Key Words
- AIEC, adherent-invasive Escherichia coli
- AJ, adherens junction
- AJC, apical junctional complex
- BP, bacterial peptidoglycans
- CD, Crohn’s disease
- CEACAM6, carcinoembryonic antigen–related cell-adhesion molecule
- IBD, inflammatory bowel disease
- IEC, intestinal epithelial cell
- IFN, interferon
- IL, interleukin
- Inflammatory Bowel Disease
- Intestinal Permeability
- JAM-A, junctional adhesion molecule-A
- LPF, long polar fimbriae
- MLC, myosin light chain
- MLCK, myosin light chain kinase
- NF-κB, nuclear factor-κB
- NOD2, nucleotide-binding oligomerization domain 2
- PDZ, PSD95-DlgA-zonula occludens-1 homology domain
- TJ, tight junction
- TNF, tumor necrosis factor
- Tight Junctions
- UC, ulcerative colitis
- ZO, zonula occludens
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Affiliation(s)
| | - Declan F. McCole
- Division of Biomedical Sciences, University of California Riverside, Riverside, California
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23
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Gavin HE, Beubier NT, Satchell KJF. The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine. PLoS Pathog 2017; 13:e1006119. [PMID: 28060924 PMCID: PMC5218395 DOI: 10.1371/journal.ppat.1006119] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 12/12/2016] [Indexed: 12/14/2022] Open
Abstract
Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX) toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD) in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs-a key step in V. vulnificus foodborne pathogenesis-even before onset of overt intestinal pathology.
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Affiliation(s)
- Hannah E. Gavin
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America
| | - Nike T. Beubier
- Department of Pathology, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, United States of America
| | - Karla J. F. Satchell
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America
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Indu VR, Lucy KM, Chungath JJ, Ashok N, Maya S. Histology and scanning electron microscopy of the tubal tonsil of goats. Vet World 2016; 8:1011-4. [PMID: 27047190 PMCID: PMC4774755 DOI: 10.14202/vetworld.2015.1011-1014] [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: 05/14/2015] [Revised: 07/17/2015] [Accepted: 07/24/2015] [Indexed: 11/16/2022] Open
Abstract
Aim: To observe the light and scanning electron microscopy (SEM) of the caprine tubal tonsil. Materials and Methods: The study was conducted on six crossbred male goats of 6 months of age. From the median sections of the head, tissue pieces from the nasopharynx around the auditory tube were collected and fixed for histology and SEM. Results: Tonsillar lymphoid tissue was located in the nasopharynx ventral to the auditory tube opening in the lateral wall of the pharynx. The height of the surface epithelium of the tubal tonsil measured 80.17±1.08 µm and was a pseudostratified ciliated columnar type with basal, supporting, and goblet cells. Above the dome of lymphoid nodules, the epithelium was modified into a follicle associated epithelium (FAE), also called lympho-epithelium or reticular epithelium and was characterized by the absence of goblet cells and cilia, reduced number of cell layers, and a large number of lymphoid cells due to interrupted basement membrane. The height of FAE was smaller than that of the surface epithelium and measured 34.33±0.92 µm. The surface of tubal tonsil showed folds and invaginations, which formed crypts. The lamina propria-submucosa underneath the epithelium was formed by the meshwork of reticular and, thin and loose collagen fibers with dome-like accumulation of lymphoid nodules. In the secondary lymphoid nodules, a corona, parafollicular area, and interfnodular area were observed. The average number of lymphoid nodules counted per field under low power magnification of microscope was 1.17±0.17, and the internodular distance was 34.00±4.37 µm. The mean diameter of lymphoid nodules was 566.67±11.45 µm and the lymphocyte count per nodule was 14741.67±174.36. The number of plasma cells counted per field under low power was 44.38±2.90 below the surface epithelium. The tubal tonsil was not encapsulated. In SEM, the surface epithelium of the tubal tonsils presented ciliated cells, microvillus (MV) cells, and goblet cells. The region of FAE possessed Type-I and Type-II MV cells and microfold (M) cells in between. Conclusion: It was concluded that the tubal tonsils were well developed in goats, which might serve as a means of protection against the spread of infection to the middle ear cavity.
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Affiliation(s)
- V R Indu
- Department of Veterinary Anatomy and Histology, College of Veterinary and Animal Sciences, Mannuthy, Kerala Veterinary and Animal Sciences University, Kerala, India
| | - K M Lucy
- Department of Veterinary Anatomy and Histology, College of Veterinary and Animal Sciences, Mannuthy, Kerala Veterinary and Animal Sciences University, Kerala, India
| | - J J Chungath
- Department of Veterinary Anatomy and Histology, College of Veterinary and Animal Sciences, Mannuthy, Kerala Veterinary and Animal Sciences University, Kerala, India
| | - N Ashok
- Department of Veterinary Anatomy and Histology, College of Veterinary and Animal Sciences, Mannuthy, Kerala Veterinary and Animal Sciences University, Kerala, India
| | - S Maya
- Department of Veterinary Anatomy and Histology, College of Veterinary and Animal Sciences, Pookode, Kerala Veterinary and Animal Sciences University, Kerala, India
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25
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Ohno H. Intestinal M cells. J Biochem 2015; 159:151-60. [PMID: 26634447 DOI: 10.1093/jb/mvv121] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Accepted: 11/27/2015] [Indexed: 11/13/2022] Open
Abstract
We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer's patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions.
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Affiliation(s)
- Hiroshi Ohno
- Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan
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26
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Wang M, Gao Z, Zhang Z, Pan L, Zhang Y. Roles of M cells in infection and mucosal vaccines. Hum Vaccin Immunother 2015; 10:3544-51. [PMID: 25483705 DOI: 10.4161/hv.36174] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The mucosal immune system plays a crucial part in the control of infection. Exposure of humans and animals to potential pathogens generally occurs through mucosal surfaces, thus, strategies that target the mucosa seem rational and efficient vaccination measures. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity compared with parenteral vaccination. M cells are capable of transporting luminal antigens to the underlying lymphoid tissues and can be exploited by pathogens as an entry portal to invade the host. Therefore, targeting M-cell-specific molecules might enhance antigen entry, initiate the immune response, and induce protection against mucosal pathogens. Here, we outline our understanding of the distribution and function of M cells, and summarize the advances in mucosal vaccine strategies that target M cells.
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Key Words
- ANX, Annexin; BALT, bronchus-associated lymphoid tissue
- C5aR, C5a receptor
- DCs, dendritic cells
- DENV, dengue virus
- EDIII, envelope domain III
- FAE, follicle-associated epithelium
- GALT, gut-associated lymphoid tissue
- GENALT, genital-associated lymphoid tissue
- GP2, Glycoprotein 2
- Hsp60, heat shock protein 60
- LPS, lipopolysaccharide
- M cells
- M cells, microfold cells
- MALT, mucosa-associated lymphoid tissue
- NALT, nasopharynx- or nose-associated lymphoid tissue
- OVA, ovalbumin
- OmpH, outer membrane protein H
- PP, Peyer's patches
- PRRs, pathogen recognition receptors
- PrPC, cellular prion protein
- SELEX, Systematic Evolution of Ligands by EXponential enrichment
- SIgA secretory IgA
- TLR-4, Toll-like receptor-4
- UEA-1,Ulex europaeus agglutinin-1
- antigen
- infection
- mucosal immunity
- pσ1, reovirus surface protein σ1
- vaccine
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Affiliation(s)
- Miao Wang
- a State Key Laboratory of Veterinary Etiological Biology; National Foot-and-Mouse Disease Reference Laboratory; Lanzhou Veterinary Research Institute; CAAS ; Lanzhou , Gansu , China
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27
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Abstract
The human body has long provided pharmaceutical science with biomaterials of interesting applications. Bile salts (BSs) are biomaterials reminiscent of traditional surfactants with peculiar structure and self-assembled topologies. In the pharmaceutical field, BSs were employed on the basis of two different concepts. The first concept exploited BSs' metabolic and homeostatic functions in disease modulation, whereas the second one utilized BSs' potential to modify drug-delivery characteristics, which recently involved nanotechnology. This review is the first to gather major pharmaceutical applications of BSs from endogenous organotropism up to integration into nanomedicine, with a greater focus on the latter domain. Endogenous applications highlighted the role of BS in modulating hypercholesterolemia and cancer therapy in view of enterohepatic circulation. In addition, recent BS-integrated nanomedicines have been surveyed, chiefly size-tunable cholate nanoparticles, BS-lecithin mixed micelles, bilosomes, probilosomes, and surface-engineered bilosomes. A greater emphasis has been laid on nanosystems for vaccine and cancer therapy. The comparative advantages of BS-integrated nanomedicines over conventional nanocarriers have been noted. Paradoxical effects, current pitfalls, future perspectives, and opinions have also been outlined.
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Affiliation(s)
- Yosra SR Elnaggar
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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28
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Min YW, Rhee PL. The Role of Microbiota on the Gut Immunology. Clin Ther 2015; 37:968-75. [DOI: 10.1016/j.clinthera.2015.03.009] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 03/09/2015] [Indexed: 12/15/2022]
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29
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Kiewiet MBG, Gros M, van Neerven RJJ, Faas MM, de Vos P. Immunomodulating properties of protein hydrolysates for application in cow's milk allergy. Pediatr Allergy Immunol 2015; 26:206-217. [PMID: 25692325 DOI: 10.1111/pai.12354] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/12/2015] [Indexed: 12/20/2022]
Abstract
Cow's milk proteins cause allergic symptoms in 2-3% of all infants. In these individuals, the tolerogenic state of the intestinal immune system is broken, which can lead to sensitization against antigens and eventually to allergic responses. Although a true treatment for food allergy is not available, symptoms can be avoided by providing the infants with hydrolyzed proteins. Hydrolyzed proteins are proteins that are enzymatically degraded. They lack typical allergenic IgE-binding epitopes but are also thought to play a pertinent role in other mechanisms inducing hypoallergenic effects. This review discusses the mechanisms and evidence for immunomodulating properties of cow's milk hydrolysates. Hydrolysates are found to strengthen the epithelial barrier, modulate T-cell differentiation, and decrease inflammation. Some studies suggest a role for hydrolysates in manipulating pathogen recognition receptors signaling as underlying mechanism. Peptides from hydrolysates have been shown to bind to TLR2 and TLR4 and influence cytokine production in epithelial cells and macrophages. Current insight suggests that hydrolysates may actively participate in modulating the immune responses in subjects with cow's milk allergy and those at risk to develop cow's milk allergy. However, more research is required to design effective and reproducible means to develop targeting strategies to modulate the immune response.
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Affiliation(s)
- M B G Kiewiet
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - M Gros
- FrieslandCampina, Amersfoort, The Netherlands
| | | | - M M Faas
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - P de Vos
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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30
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Mycobacterium tuberculosis
infection of the ‘non‐classical immune cell’. Immunol Cell Biol 2015; 93:789-95. [PMID: 25801479 DOI: 10.1038/icb.2015.43] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 03/02/2015] [Accepted: 03/18/2015] [Indexed: 01/29/2023]
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31
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Jiang PL, Lin HJ, Wang HW, Tsai WY, Lin SF, Chien MY, Liang PH, Huang YY, Liu DZ. Galactosylated liposome as a dendritic cell-targeted mucosal vaccine for inducing protective anti-tumor immunity. Acta Biomater 2015; 11:356-67. [PMID: 25242652 DOI: 10.1016/j.actbio.2014.09.019] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 09/02/2014] [Accepted: 09/12/2014] [Indexed: 01/08/2023]
Abstract
Mucosal surfaces contain specialized dendritic cells (DCs) that are able to recognize foreign pathogens and mount protective immunity. We previously demonstrated that intranasal administration of targeted galactosylated liposomes can elicit mucosal and systemic antibody responses. In the present study, we assessed whether galactosylated liposomes could act as an effective DC-targeted mucosal vaccine that would be capable of inducing systemic anti-tumor immunity as well as antibody responses. We show that targeted galactosylated liposomes effectively facilitated antigen uptake by DCs beyond that mediated by unmodified liposomes both in vitro and in vivo. Targeted galactosylated liposomes induced higher levels of pro-inflammatory cytokines than unmodified liposomes in vitro. C57BL/6 mice thrice immunized intranasally with ovalbumin (OVA)-encapsulated galactosylated liposomes produced high levels of OVA-specific IgG antibodies in their serum. Spleen cells from mice receiving galactosylated liposomes were restimulated with OVA and showed significantly augmented levels of IFN-γ, IL-4, IL-5 and IL-6. In addition, intranasal administration of OVA-encapsulated beta-galactosylated liposomes resulted in complete protection against EG7 tumor challenge in C57BL/6 mice. Taken together, these results indicate that nasal administration of a galactosylated liposome vaccine mediates the development of an effective immunity against tumors and might be useful for further clinical anti-tumoral applications.
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32
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33
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Vautier S, Drummond RA, Chen K, Murray GI, Kadosh D, Brown AJP, Gow NAR, MacCallum DM, Kolls JK, Brown GD. Candida albicans colonization and dissemination from the murine gastrointestinal tract: the influence of morphology and Th17 immunity. Cell Microbiol 2014; 17:445-50. [PMID: 25346172 PMCID: PMC4409086 DOI: 10.1111/cmi.12388] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 10/13/2014] [Accepted: 10/21/2014] [Indexed: 12/15/2022]
Abstract
The ability of Candida albicans to cause disease is associated with its capacity to undergo morphological transition between yeast and filamentous forms, but the role of morphology in colonization and dissemination from the gastrointestinal (GI) tract remains poorly defined. To explore this, we made use of wild-type and morphological mutants of C. albicans in an established model of GI tract colonization, induced following antibiotic treatment of mice. Our data reveal that GI tract colonization favours the yeast form of C. albicans, that there is constitutive low level systemic dissemination in colonized mice that occurs irrespective of fungal morphology, and that colonization is not controlled by Th17 immunity in otherwise immunocompetent animals. These data provide new insights into the mechanisms of pathogenesis and commensalism of C. albicans, and have implications for our understanding of human disease.
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Affiliation(s)
- Simon Vautier
- Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, UK
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34
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McDermott AJ, Huffnagle GB. The microbiome and regulation of mucosal immunity. Immunology 2014; 142:24-31. [PMID: 24329495 DOI: 10.1111/imm.12231] [Citation(s) in RCA: 224] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 11/01/2013] [Accepted: 11/19/2013] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal tract is a mucosal surface constantly exposed to foreign antigens and microbes, and is protected by a vast array of immunologically active structures and cells. Epithelial cells directly participate in immunological surveillance and direction of host responses in the gut and can express numerous pattern recognition receptors, including Toll-like receptor 5 (TLR5), TLR1, TLR2, TLR3, TLR9, and nucleotide oligomerization domain 2, as well as produce chemotactic factors for both myeloid and lymphoid cells following inflammatory stimulation. Within the epithelium and in the underlying lamina propria resides a population of innate lymphoid cells that, following stimulation, can become activated and produce effector cytokines and exert both protective and pathogenic roles during inflammation. Lamina propria dendritic cells play a large role in determining whether the response to a particular antigen will be inflammatory or anti-inflammatory. It is becoming clear that the composition and metabolic activity of the intestinal microbiome, as a whole community, exerts a profound influence on mucosal immune regulation. The microbiome produces short-chain fatty acids, polysaccharide A, α-galactosylceramide and tryptophan metabolites, which can induce interleukin-22, Reg3γ, IgA and interleukin-17 responses. However, much of what is known about microbiome-host immune interactions has come from the study of single bacterial members of the gastrointestinal microbiome and their impact on intestinal mucosal immunity. Additionally, evidence continues to accumulate that alterations of the intestinal microbiome can impact not only gastrointestinal immunity but also immune regulation at distal mucosal sites.
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Affiliation(s)
- Andrew J McDermott
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA
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35
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Abstract
The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells.
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36
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Finn R, Ahmad T, Coffey ET, Brayden DJ, Baird AW, Boyd A. Translocation ofVibrio parahaemolyticusacross anin vitroM cell model. FEMS Microbiol Lett 2013; 350:65-71. [DOI: 10.1111/1574-6968.12323] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 09/27/2013] [Accepted: 10/30/2013] [Indexed: 12/13/2022] Open
Affiliation(s)
- Rebecca Finn
- Discipline of Microbiology; National University of Ireland; Galway Ireland
| | - Tauseef Ahmad
- School of Veterinary Medicine; Veterinary Science Centre; University College Dublin; Dublin Ireland
| | - Eleanor T. Coffey
- Turku Centre for Biotechnology; Turku University and Åbo Akademi University; Turku Finland
| | - David J. Brayden
- School of Veterinary Medicine; Veterinary Science Centre; University College Dublin; Dublin Ireland
| | - Alan W. Baird
- School of Veterinary Medicine; Veterinary Science Centre; University College Dublin; Dublin Ireland
| | - Aoife Boyd
- Discipline of Microbiology; National University of Ireland; Galway Ireland
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37
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Yeboah KG, Akande J, Addo RT, Siwale RC, Aninkorah-Yeboah K, Siddig A. In vitroandex vivocharacterization of lectin-labeledMycobacterium tuberculosisantigen-containing microspheres for enhanced oral delivery. J Drug Target 2013; 22:34-47. [DOI: 10.3109/1061186x.2013.833206] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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38
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Reineke JJ, Cho DY, Dingle YT, Morello AP, Jacob J, Thanos CG, Mathiowitz E. Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres. Proc Natl Acad Sci U S A 2013; 110:13803-8. [PMID: 23922388 PMCID: PMC3752225 DOI: 10.1073/pnas.1305882110] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 µm) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (≤ 5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 µm) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine.
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Affiliation(s)
- Joshua J. Reineke
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202; and
| | - Daniel Y. Cho
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912
| | - Yu-Ting Dingle
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912
| | - A. Peter Morello
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912
| | - Jules Jacob
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912
| | - Christopher G. Thanos
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912
| | - Edith Mathiowitz
- Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912
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39
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Casteleyn C, Van den Broeck W, Gebert A, Tambuyzer BR, Van Cruchten S, Van Ginneken C. M cell specific markers in man and domestic animals: Valuable tools in vaccine development. Comp Immunol Microbiol Infect Dis 2013; 36:353-64. [DOI: 10.1016/j.cimid.2013.03.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Revised: 03/01/2013] [Accepted: 03/21/2013] [Indexed: 12/13/2022]
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40
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Erysipelothrix rhusiopathiae exploits cytokeratin 18-positive epithelial cells of porcine tonsillar crypts as an invasion gateway. Vet Immunol Immunopathol 2013; 153:260-6. [DOI: 10.1016/j.vetimm.2013.03.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2012] [Revised: 03/15/2013] [Accepted: 03/20/2013] [Indexed: 11/20/2022]
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41
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Abstract
Immunotherapy, in recent times, has found its application in a variety of immunologically mediated diseases. Oral immunotherapy may not only increase patient compliance but may, in particular, also induce both systemic as well as mucosal immune responses, due to mucosal application of active agents. To improve the bioavailability and to trigger strong immunological responses, recent research projects focused on the encapsulation of drugs and antigens into polymer particles. These particles protect the loaded antigen from the harsh conditions in the GI tract. Furthermore, modification of the surface of particles by the use of lectins, such as Aleuria aurantia lectin, wheatgerm agglutinin or Ulex europaeus-I, enhances the binding to epithelial cells, in particular to membranous cells, of the mucosa-associated lymphoid tissue. Membranous cell-specific targeting leads to an improved transepithelial transport of the particle carriers. Thus, enhanced uptake and presentation of the encapsulated antigen by antigen-presenting cells favor strong systemic, but also local, mucosal immune responses.
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42
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Tobias J, Svennerholm AM. Strategies to overexpress enterotoxigenic Escherichia coli (ETEC) colonization factors for the construction of oral whole-cell inactivated ETEC vaccine candidates. Appl Microbiol Biotechnol 2012; 93:2291-300. [DOI: 10.1007/s00253-012-3930-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Revised: 01/27/2012] [Accepted: 01/28/2012] [Indexed: 11/25/2022]
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43
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Kohl KD. Diversity and function of the avian gut microbiota. J Comp Physiol B 2012; 182:591-602. [PMID: 22246239 DOI: 10.1007/s00360-012-0645-z] [Citation(s) in RCA: 187] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2011] [Revised: 12/30/2011] [Accepted: 01/04/2012] [Indexed: 01/16/2023]
Abstract
The intestinal microbiota have now been shown to largely affect host health through various functional roles in terms of nutrition, immunity, and other physiological systems. However, the majority of these studies have been carried out in mammalian hosts, which differ in their physiological traits from other taxa. For example, birds possess several unique life history traits, such as hatching from eggs, which may alter the interactions with and transmission of intestinal microbes compared to most mammals. This review covers the diversity of microbial taxa hosted by birds. It also discusses how avian microbial communities strongly influence nutrition, immune function, and processing of toxins in avian hosts, in manners similar to and different from mammalian systems. Finally, areas demanding further research are identified, along with descriptions of existing techniques that could be employed to answer these questions.
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Affiliation(s)
- Kevin D Kohl
- Department of Biology, University of Utah, 257 S. 1400 East, Salt Lake City, UT, 84112, USA.
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44
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Fukuda S, Hase K, Ohno H. Application of a mouse ligated Peyer’s patch intestinal loop assay to evaluate bacterial uptake by M cells. J Vis Exp 2011:3225. [PMID: 22215009 DOI: 10.3791/3225] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
The inside of our gut is inhabited with enormous number of commensal bacteria. The mucosal surface of the gastrointestinal tract is continuously exposed to them and occasionally to pathogens. The gut-associated lymphoid tissue (GALT) play a key role for induction of the mucosal immune response to these microbes. To initiate the mucosal immune response, the mucosal antigens must be transported from the gut lumen across the epithelial barrier into organized lymphoid follicles such as Peyer's patches. This antigen transcytosis is mediated by specialized epithelial M cells. M cells are atypical epithelial cells that actively phagocytose macromolecules and microbes. Unlike dendritic cells (DCs) and macrophages, which target antigens to lysosomes for degradation, M cells mainly transcytose the internalized antigens. This vigorous macromolecular transcytosis through M cells delivers antigen to the underlying organized lymphoid follicles and is believed to be essential for initiating antigen-specific mucosal immune responses. However, the molecular mechanisms promoting this antigen uptake by M cells are largely unknown. We have previously reported that glycoprotein 2 (Gp2), specifically expressed on the apical plasma membrane of M cells among enterocytes, serves as a transcytotic receptor for a subset of commensal and pathogenic enterobacteria, including Escherichia coli and Salmonella enterica serovar Typhimurium (S. Typhimurium), by recognizing FimH, a component of type I pili on the bacterial outer membrane. Here, we present a method for the application of a mouse Peyer's patch intestinal loop assay to evaluate bacterial uptake by M cells. This method is an improved version of the mouse intestinal loop assay previously described. The improved points are as follows: 1. Isoflurane was used as an anesthetic agent. 2. Approximately 1 cm ligated intestinal loop including Peyer's patch was set up. 3. Bacteria taken up by M cells were fluorescently labeled by fluorescence labeling reagent or by overexpressing fluorescent protein such as green fluorescent protein (GFP). 4. M cells in the follicle-associated epithelium covering Peyer's patch were detected by whole-mount immunostainig with anti Gp2 antibody. 5. Fluorescent bacterial transcytosis by M cells were observed by confocal microscopic analysis. The mouse Peyer's patch intestinal loop assay could supply the answer what kind of commensal or pathogenic bacteria transcytosed by M cells, and may lead us to understand the molecular mechanism of how to stimulate mucosal immune system through M cells.
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Affiliation(s)
- Shinji Fukuda
- Laboratory for Epithelial Immunobiology, RIKEN Research Center for Allergy and Immunology
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45
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Abstract
The ability of Vibrio cholerae to persist in bodies of water will continue to confound our ability to eradicate cholera through improvements to infrastructure, and thus cholera vaccines are needed. We aim for an inexpensive vaccine that can provide long-lasting protection from all epidemic cholera infections, currently caused by O1 or O139 serogroups. Recent insights into correlates of protection, epidemiology and pathogenesis may help us design improved vaccines. This notwithstanding, we have come to appreciate that even marginally protective vaccines, such as oral whole-cell killed vaccines, if widely distributed, can provide significant protection, owing to herd immunity. Further efforts are still required to provide more effective protection of young children.
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Affiliation(s)
- Anne L Bishop
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, MA 02111, USA
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46
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Salim SY, Söderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis 2011; 17:362-81. [PMID: 20725949 DOI: 10.1002/ibd.21403] [Citation(s) in RCA: 424] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Accepted: 06/01/2010] [Indexed: 12/12/2022]
Abstract
The current paradigm of inflammatory bowel diseases (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), involves the interaction between environmental factors in the intestinal lumen and inappropriate host immune responses in genetically predisposed individuals. The intestinal mucosal barrier has evolved to maintain a delicate balance between absorbing essential nutrients while preventing the entry and responding to harmful contents. In IBD, disruptions of essential elements of the intestinal barrier lead to permeability defects. These barrier defects exacerbate the underlying immune system, subsequently resulting in tissue damage. The epithelial phenotype in active IBD is very similar in CD and UC. It is characterized by increased secretion of chloride and water, leading to diarrhea, increased permeability via both the transcellular and paracellular routes, and increased apoptosis of epithelial cells. The main cytokine that seems to drive these changes is tumor necrosis factor alpha in CD, whereas interleukin (IL)-13 may be more important in UC. Therapeutic restoration of the mucosal barrier would provide protection and prevent antigenic overload due to intestinal "leakiness." Here we give an overview of the key players of the intestinal mucosal barrier and review the current literature from studies in humans and human systems on mechanisms underlying mucosal barrier dysfunction in IBD.
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Affiliation(s)
- Sa'ad Y Salim
- Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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47
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Friswell M, Campbell B, Rhodes J. The role of bacteria in the pathogenesis of inflammatory bowel disease. Gut Liver 2010; 4:295-306. [PMID: 20981205 DOI: 10.5009/gnl.2010.4.3.295] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Accepted: 04/06/2010] [Indexed: 12/19/2022] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) have features that suggest bacterial involvement, and all genetic models of inflammatory bowel disease (IBD) require the presence of commensal bacteria. CD is associated with innate immune response genes such as NOD2/CARD15 and the autophagy genes ATG16L1 and IRGM. However, IBD responds to immunosuppression, suggesting that any bacteria involved are not acting as conventional pathogens. Molecular techniques are rapidly advancing our knowledge of the gut microbiota. In CD there is reduced diversity, and notably a reduction in the probiotic Faecalibacterium prausnitzii, the presence of which in the terminal ileum is associated with a reduced risk of recurrence following surgery. There is also a consistent increase in mucosa-associated Escherichia coli with an "adherent and invasive" phenotype, which allows them to replicate inside macrophages and induce granulomas. Speculation that CD could be caused by the Mycobacterium avium subspecies paratuberculosis (MAP) continues. The response to antitumor necrosis factor treatments suggests that, if relevant at all, MAP is not acting as a conventional pathogen. However, there is increased colonization by MAP in CD, and there is evidence that it could have an indirect effect mediated by the suppression of macrophage function. UC relapse is frequently associated with infection by pathogens, but there is less evidence for involvement of a specific bacterial species. Poor barrier integrity followed by an inflammatory reaction to bacterial components, with chronicity maintained by an autoimmune process, seems a plausible pathogenic model. Bacterial theories of pathogenesis are now becoming testable by targeted therapeutic interventions.
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Affiliation(s)
- Melissa Friswell
- Gastroenterology Research Unit, University of Liverpool School of Clinical Sciences, Liverpool, UK
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48
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Mantis NJ, Forbes SJ. Secretory IgA: arresting microbial pathogens at epithelial borders. Immunol Invest 2010; 39:383-406. [PMID: 20450284 DOI: 10.3109/08820131003622635] [Citation(s) in RCA: 133] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Secretory IgA (SIgA) is the predominant class of antibody found in intestinal secretions. Although SIgA's role in protecting the intestinal epithelium from the enteric pathogens and toxins has long been recognized, surprisingly little is known about the molecular mechanisms by which this is achieved. The present review summarizes the current understanding of how SIgA functions to prevent microbial pathogens and toxins from gaining access to the intestinal epithelium. We also discuss recent work from our laboratory examining the interaction of a particular protective monoclonal IgA with Salmonella and propose, based on this work, that SIgA has a previously unrecognized capacity to directly interfere with microbial virulence at mucosal surfaces.
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Affiliation(s)
- Nicholas J Mantis
- Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, University at Albany School of Public Health, Albany, New York 12208, USA.
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49
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Keita AV, Söderholm JD, Ericson AC. Stress-induced barrier disruption of rat follicle-associated epithelium involves corticotropin-releasing hormone, acetylcholine, substance P, and mast cells. Neurogastroenterol Motil 2010; 22:770-8, e221-2. [PMID: 20149111 DOI: 10.1111/j.1365-2982.2010.01471.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The follicle-associated epithelium (FAE) is specialized in uptake and sampling of luminal antigens and bacteria. We previously showed that stress increased FAE permeability in rats. An increased uptake may alter antigen exposure in Peyer's patches leading to intestinal disease. The aim of this study was to elucidate mechanisms involved in the acute stress-induced increase in FAE permeability. METHODS Rats were pretreated i.p. with corticotropin-releasing hormone receptor (CRH-R) antagonist, neurokinin receptor 1 (NK-1R) antagonist, atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to 1-h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for measurements of permeability to (51)Cr-EDTA, horseradish peroxidase (HRP) and chemically killed Escherichia coli K-12. Further, FAE segments were exposed in vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter- and receptor distribution was studied by immunohistochemistry. KEY RESULTS Stress-induced increases in uptake across FAE of HRP and E. coli were reduced by DOX, CRH-R antagonist and atropine, whereas the NK-1R antagonist decreased (51)Cr-EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli passage, whereas SP increased bacterial and (51)Cr-EDTA permeability. DOX counteracted all of these effects. Immunohistochemistry revealed CRH, acetylcholine, SP, and their receptors on mast cells within the Peyer's patches, subepithelial dome, and adjacent villi. CONCLUSIONS & INFERENCES Corticotropin-releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress-related intestinal disorders.
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Affiliation(s)
- A V Keita
- Division of Surgery and Clinical Oncology, Department of Clinical and Experimental Medicine, Clinical and Experimental Research, Faculty of Health Science, University Hospital, Linköping, Sweden
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Abstract
BACKGROUND The ability to control uptake across the mucosa and protect from damage of harmful substances from the lumen is defined as intestinal barrier function. A disturbed barrier dysfunction has been described in many human diseases and animal models, for example, inflammatory bowel disease, irritable bowel syndrome, and intestinal hypersensitivity. In most diseases and models, alterations are seen both of the paracellular pathway, via the tight junctions, and of the transcellular routes, via different types of endocytosis. Recent studies of pathogenic mechanisms have demonstrated the important role of neuroimmune interaction with the epithelial cells in the regulation of barrier function. Neural impulses from extrinsic vagal and/or sympathetic efferent fibers or intrinsic enteric nerves influence mucosal barrier function via direct effects on epithelial cells or via interaction with immune cells. For example, by nerve-mediated activation by corticotropin-releasing hormone or cholinergic pathways, mucosal mast cells release a range of mediators with effects on transcellular, and/or paracellular permeability (for example, tryptase, TNF-alpha, nerve growth factor, and interleukins). PURPOSE In this review, we discuss current physiological and pathophysiological aspects of the intestinal barrier and, in particular, its regulation by neuroimmune factors.
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Affiliation(s)
- A V Keita
- Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Faculty of Health Science, University Hospital, Linköping, Sweden
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