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Hiney K, Sypniewski L, DeSilva U, Pezeshki A, Rudra P, Goodarzi P, Willis E, McFarlane D. Fecal microbiota composition, serum metabolomics, and markers of inflammation in dogs fed a raw meat-based diet compared to those on a kibble diet. Front Vet Sci 2024; 11:1328513. [PMID: 38694479 PMCID: PMC11061498 DOI: 10.3389/fvets.2024.1328513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 03/13/2024] [Indexed: 05/04/2024] Open
Abstract
Introduction Despite the potential health risks associated with feeding raw and non-traditional diets, the use of these diets in dogs is increasing, yet the health outcomes associated with these diets is not well understood. This study investigates the effect of feeding dogs a kibble or raw meat-based diets on fecal microbiota composition, serum metabolomics and inflammatory markers. Methods Clinically healthy dogs with a history of consuming either kibble (KD, n = 27) or raw meat-based diets (RMBD, n = 28) for more than 1 year were enrolled. Dogs were fed a standardized diet of either a single brand of KD or RMBD for 28 days. Serum and fecal samples were collected for analysis of microbiota, metabolomics, and inflammatory markers. Multiple regression analysis was performed for each of the metabolites and inflammatory markers, with feed group, age and BCS included as independent variables. Results The fecal microbiota composition differed between the KD and RMBD groups. Beta-diversity and some indices of alpha-diversity (i.e., Shannon and Simpson) were different between the two diet groups. Sixty- three serum metabolites differed between KD and RMBD-fed dogs with the majority reflecting the differences in macronutrient composition of the two diets.Fecal IAP, IgG and IgA were significantly higher in RMBD dogs compared to KD dogs, while systemic markers of inflammation, including serum c-reactive protein (CRP), galectin, secretory receptor of advanced glycation end-products (sRAGE), haptoglobin, and serum IgG were similar in dogs fed either diet. Discussion Diet composition significantly affected fecal microbiota composition and metabolome. Although it had a potentially beneficial effect on local inflammatory markers, feeding RMBD had no impact on systemic inflammation. The influence of these changes on long term health outcomes provides an area for future study.
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Affiliation(s)
- Kris Hiney
- Department of Animal and Food Sciences, Ferguson College of Agriculture, Oklahoma State University, Stillwater, OK, United States
| | - Lara Sypniewski
- Department of Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, United States
| | - Udaya DeSilva
- Department of Animal and Food Sciences, Ferguson College of Agriculture, Oklahoma State University, Stillwater, OK, United States
| | - Adel Pezeshki
- Department of Animal and Food Sciences, Ferguson College of Agriculture, Oklahoma State University, Stillwater, OK, United States
| | - Pratyaydipta Rudra
- Department of Statistics, College of Arts and Sciences, Oklahoma State University, Stillwater, OK, United States
| | - Parniyan Goodarzi
- Department of Animal and Food Sciences, Ferguson College of Agriculture, Oklahoma State University, Stillwater, OK, United States
| | - Erin Willis
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, United States
| | - Dianne McFarlane
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, United States
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States
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Shemtov SJ, Emani R, Bielska O, Covarrubias AJ, Verdin E, Andersen JK, Winer DA. The intestinal immune system and gut barrier function in obesity and ageing. FEBS J 2023; 290:4163-4186. [PMID: 35727858 PMCID: PMC9768107 DOI: 10.1111/febs.16558] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 04/29/2022] [Accepted: 06/20/2022] [Indexed: 08/13/2023]
Abstract
Obesity and ageing predispose to numerous, yet overlapping chronic diseases. For example, metabolic abnormalities, including insulin resistance (IR) and type 2 diabetes (T2D) are important causes of morbidity and mortality. Low-grade chronic inflammation of tissues, such as the liver, visceral adipose tissue and neurological tissues, is considered a significant contributor to these chronic diseases. Thus, it is becoming increasingly important to understand what drives this inflammation in affected tissues. Recent evidence, especially in the context of obesity, suggests that the intestine plays an important role as the gatekeeper of inflammatory stimuli that ultimately fuels low-grade chronic tissue inflammation. In addition to metabolic diseases, abnormalities in the intestinal mucosal barrier have been linked to a range of other chronic inflammatory conditions, such as neurodegeneration and ageing. The flow of inflammatory stimuli from the gut is in part controlled by local immunological inputs impacting the intestinal barrier. Here, we will review the impact of obesity and ageing on the intestinal immune system and its downstream consequences on gut barrier function, which is strongly implicated in the pathogenesis of obesity and age-related diseases. In particular, we will discuss the effects of age-related intestinal dysfunction on neurodegenerative diseases.
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Affiliation(s)
- Sarah J. Shemtov
- Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA
- Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
| | - Rohini Emani
- Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
| | - Olga Bielska
- Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
| | - Anthony J. Covarrubias
- Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095 USA
- Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095 USA
| | - Eric Verdin
- Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
| | - Julie K. Andersen
- Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
| | - Daniel A. Winer
- Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA
- Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
- Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON, M5G 1L7, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada
- Department of Immunology, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada
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Untersmayr E, Brandt A, Koidl L, Bergheim I. The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging. Nutrients 2022; 14:949. [PMID: 35267924 PMCID: PMC8912763 DOI: 10.3390/nu14050949] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 02/17/2022] [Accepted: 02/21/2022] [Indexed: 12/13/2022] Open
Abstract
The intestinal barrier, composed of the luminal microbiota, the mucus layer, and the physical barrier consisting of epithelial cells and immune cells, the latter residing underneath and within the epithelial cells, plays a special role in health and disease. While there is growing knowledge on the changes to the different layers associated with disease development, the barrier function also plays an important role during aging. Besides changes in the composition and function of cellular junctions, the entire gastrointestinal physiology contributes to essential age-related changes. This is also reflected by substantial differences in the microbial composition throughout the life span. Even though it remains difficult to define physiological age-related changes and to distinguish them from early signs of pathologies, studies in centenarians provide insights into the intestinal barrier features associated with longevity. The knowledge reviewed in this narrative review article might contribute to the definition of strategies to prevent the development of diseases in the elderly. Thus, targeted interventions to improve overall barrier function will be important disease prevention strategies for healthy aging in the future.
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Affiliation(s)
- Eva Untersmayr
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
| | - Annette Brandt
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria;
| | - Larissa Koidl
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
| | - Ina Bergheim
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria;
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Enterocytozoon schreckii n. sp. Infects the Enterocytes of Adult Chinook Salmon ( Oncorhynchus tshawytscha) and May Be a Sentinel of Immunosenescence. mSphere 2022; 7:e0090821. [PMID: 34986317 PMCID: PMC8730814 DOI: 10.1128/msphere.00908-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
A novel Enterocytozoon infection was identified in the intestines of sexually mature Chinook salmon. While microsporidian parasites are common across a diverse range of animal hosts, this novel species is remarkable because it demonstrates biological, pathological, and genetic similarity with Enterocytozoon bieneusi, the most common causative agent of microsporidiosis in AIDS patients. There are similarities in the immune and endocrine processes of sexually mature Pacific salmon and immunocompromised humans, suggesting possible common mechanisms of susceptibility in these two highly divergent host species. The discovery of Enterocytozoon schreckii n. sp. contributes to clarifying the phylogenetic relationships within family Enterocytozoonidae. The phylogenetic and morphological features of this species support the redescription of Enterocytozoon to include Enterospora as a junior synonym. Furthermore, the discovery of this novel parasite may have important implications for conservation, as it could be a sentinel of immune suppression, disease, and prespawning mortality in threatened populations of salmonids. IMPORTANCE In this work, we describe a new microsporidian species that infects the enterocytes of Chinook salmon. This novel pathogen is closely related to Enterocytozoon bieneusi, an opportunistic pathogen commonly found in AIDS patients and other severely immunocompromised humans. The discovery of this novel pathogen is of interest because it has only been found in sexually mature Chinook salmon, which have compromised immune systems due to the stresses of migration and maturation and which share similar pathological features with immunocompromised and senescent humans. The discovery of this novel pathogen could lead to new insights regarding how microsporidiosis relates to immunosuppression across animal hosts.
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Barroso FAL, de Jesus LCL, de Castro CP, Batista VL, Ferreira Ê, Fernandes RS, de Barros ALB, Leclerq SY, Azevedo V, Mancha-Agresti P, Drumond MM. Intake of Lactobacillus delbrueckii (pExu: hsp65) Prevents the Inflammation and the Disorganization of the Intestinal Mucosa in a Mouse Model of Mucositis. Microorganisms 2021; 9:microorganisms9010107. [PMID: 33466324 PMCID: PMC7824804 DOI: 10.3390/microorganisms9010107] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 11/24/2020] [Accepted: 11/30/2020] [Indexed: 02/07/2023] Open
Abstract
5-Fluorouracil (5-FU) is an antineoplastic drug that causes, as a side effect, intestinal mucositis, acute inflammation in the small bowel. The Heat Shock Protein (Hsp) are highly expressed in inflammatory conditions, developing an important role in immune modulation. Thus, they are potential candidates for the treatment of inflammatory diseases. In the mucositis mouse model, the present study aimed to evaluate the beneficial effect of oral administration of milk fermented by Lactobacillus delbrueckii CIDCA 133 (pExu:hsp65), a recombinant strain. This approach showed increased levels of sIgA in the intestinal fluid, reducing inflammatory infiltrate and intestinal permeability. Additionally, the histological score was improved. Protection was associated with a reduction in the gene expression of pro-inflammatory cytokines such as Tnf, Il6, Il12, and Il1b, and an increase in Il10, Muc2, and claudin 1 (Cldn1) and 2 (Cldn2) gene expression in ileum tissue. These findings are corroborated with the increased number of goblet cells, the electronic microscopy images, and the reduction of intestinal permeability. The administration of milk fermented by this recombinant probiotic strain was also able to reverse the high levels of gene expression of Tlrs caused by the 5-FU. Thus, the rCIDCA 133:Hsp65 strain was revealed to be a promising preventive strategy for small bowel inflammation.
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Affiliation(s)
- Fernanda Alvarenga Lima Barroso
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
| | - Luís Cláudio Lima de Jesus
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
| | - Camila Prosperi de Castro
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
| | - Viviane Lima Batista
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
| | - Ênio Ferreira
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil;
| | - Renata Salgado Fernandes
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Campus da UFMG, Universidade Federal de Minas Gerais, Cidade Universitária, Belo Horizonte 31270-901, Brazil; (R.S.F.); (A.L.B.d.B.)
| | - André Luís Branco de Barros
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Campus da UFMG, Universidade Federal de Minas Gerais, Cidade Universitária, Belo Horizonte 31270-901, Brazil; (R.S.F.); (A.L.B.d.B.)
| | - Sophie Yvette Leclerq
- Laboratório de Inovação Biotecnológica, Fundação Ezequiel Dias (FUNED), Belo Horizonte 30510-010, Brazil;
| | - Vasco Azevedo
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
| | - Pamela Mancha-Agresti
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
- Faculdade de Minas-Faminas-BH, Medicina, Belo Horizonte 31744-007, Brazil
- Correspondence: (P.M.-A.); (M.M.D.); Tel.: +55-31-99817-5004 (P.M.-A.); +55-31-99222-2761 (M.M.D.)
| | - Mariana Martins Drumond
- Laboratório de Genética Celular e Molecular (LGCM), Departamento de—Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil; (F.A.L.B.); (L.C.L.d.J.); (C.P.d.C.); (V.L.B.); (V.A.)
- Centro Federal de Educação Tecnológica de Minas Gerais (CEFET/MG), Departamento de Ciências Biológicas, Belo Horizonte 31421-169, Brazil
- Correspondence: (P.M.-A.); (M.M.D.); Tel.: +55-31-99817-5004 (P.M.-A.); +55-31-99222-2761 (M.M.D.)
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Age-related chemokine alterations affect IgA secretion and gut immunity in female mice. Biogerontology 2020; 21:609-618. [DOI: 10.1007/s10522-020-09877-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 03/30/2020] [Indexed: 01/09/2023]
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Probiotic Propionibacterium freudenreichii requires SlpB protein to mitigate mucositis induced by chemotherapy. Oncotarget 2019; 10:7198-7219. [PMID: 31921383 PMCID: PMC6944450 DOI: 10.18632/oncotarget.27319] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023] Open
Abstract
Propionibacterium freudenreichii CIRM-BIA 129 (P. freudenreichii wild type, WT) is a probiotic bacterium, which exerts immunomodulatory effects. This strain possesses extractable surface proteins, including SlpB, which are involved in anti-inflammatory effect and in adhesion to epithelial cells. We decided to investigate the impact of slpB gene mutation on immunomodulation in vitro and in vivo. In an in vitro assay, P. freudenreichii WT reduced expression of IL-8 (p<0.0001) and TNF-α (p<0.0001) cytokines in LPS-stimulated HT-29 cells. P. freudenreichii ΔslpB, lacking the SlpB protein, failed to do so. Subsequently, both strains were investigated in vivo in a 5-FU-induced mucositis mice model. Mucositis is a common side effect of cytotoxic chemotherapy with 5-FU, characterized by mucosal injury, inflammation, diarrhea, and weight loss. The WT strain prevented weight loss, reduced inflammation and consequently histopathological scores. Furthermore, it regulated key markers, including Claudin-1 (cld1, p<0.0005) and IL-17a (Il17a, p<0.0001) genes, as well as IL-12 (p<0.0001) and IL-1β (p<0.0429) cytokines levels. Mutant strain displayed opposite regulatory effect on cld1 expression and on IL-12 levels. This work emphasizes the importance of SlpB in P. freudenreichii ability to reduce mucositis inflammation. It opens perspectives for the development of probiotic products to decrease side effects of chemotherapy using GRAS bacteria with immunomodulatory surface protein properties.
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8
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Branca JJ, Gulisano M, Nicoletti C. Intestinal epithelial barrier functions in ageing. Ageing Res Rev 2019; 54:100938. [PMID: 31369869 DOI: 10.1016/j.arr.2019.100938] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 07/19/2019] [Accepted: 07/24/2019] [Indexed: 12/11/2022]
Abstract
The intestinal epithelial barrier protects the mucosa of the gastrointestinal (GI)-tract and plays a key role in maintaining the host homeostasis. It encompasses several elements that include the intestinal epithelium and biochemical and immunological products, such as the mucus layer, antimicrobial peptides (AMPs) and secretory immunologlobulin A (sIgA). These components are interlinked with the large microbial community inhabiting the gut to form a highly sophisticated biological system that plays an important role on many aspects of human health both locally and systemically. Like any other organ and tissue, the intestinal epithelial barrier is affected by the ageing process. New insights have surfaced showing that critical functions, including intestinal stem cell regeneration and regulation of the intestinal crypt homeostasis, barrier integrity, production of regulatory cytokines, and epithelial innate immunity to pathogenic antigens change across life. Here we review the age-associated changes of the various components of the intestinal epithelial barrier and we highlight the necessity to elucidate further the mechanisms underlying these changes. Expanding our knowledge in this area is a goal of high medical relevance and it will help to define intervention strategies to ameliorate the quality of life of the ever-expanding elderly population.
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Osorio C, Kanukuntla T, Diaz E, Jafri N, Cummings M, Sfera A. The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling. Front Aging Neurosci 2019; 11:143. [PMID: 31297054 PMCID: PMC6608545 DOI: 10.3389/fnagi.2019.00143] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 05/29/2019] [Indexed: 12/14/2022] Open
Abstract
The amyloid hypothesis, the assumption that beta-amyloid toxicity is the primary cause of neuronal and synaptic loss, has been the mainstream research concept in Alzheimer's disease for the past two decades. Currently, this model is quietly being replaced by a more holistic, “systemic disease” paradigm which, like the aging process, affects multiple body tissues and organs, including the gut microbiota. It is well-established that inflammation is a hallmark of cellular senescence; however, the infection-senescence link has been less explored. Microbiota-induced senescence is a gradually emerging concept promoted by the discovery of pathogens and their products in Alzheimer's disease brains associated with senescent neurons, glia, and endothelial cells. Infectious agents have previously been associated with Alzheimer's disease, but the cause vs. effect issue could not be resolved. A recent study may have settled this debate as it shows that gingipain, a Porphyromonas gingivalis toxin, can be detected not only in Alzheimer's disease but also in the brains of older individuals deceased prior to developing the illness. In this review, we take the position that gut and other microbes from the body periphery reach the brain by triggering intestinal and blood-brain barrier senescence and disruption. We also surmise that novel Alzheimer's disease findings, including neuronal somatic mosaicism, iron dyshomeostasis, aggressive glial phenotypes, and loss of aerobic glycolysis, can be explained by the infection-senescence model. In addition, we discuss potential cellular senescence targets and therapeutic strategies, including iron chelators, inflammasome inhibitors, senolytic antibiotics, mitophagy inducers, and epigenetic metabolic reprograming.
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Affiliation(s)
- Carolina Osorio
- Psychiatry, Loma Linda University, Loma Linda, CA, United States
| | - Tulasi Kanukuntla
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
| | - Eddie Diaz
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
| | - Nyla Jafri
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
| | - Michael Cummings
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
| | - Adonis Sfera
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
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De Jesus LCL, Drumond MM, de Carvalho A, Santos SS, Martins FS, Ferreira Ê, Fernandes RS, de Barros ALB, do Carmo FL, Perez PF, Azevedo V, Mancha-Agresti P. Protective effect of Lactobacillus delbrueckii subsp. Lactis CIDCA 133 in a model of 5 Fluorouracil-Induced intestinal mucositis. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.12.027] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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García-Peña C, Álvarez-Cisneros T, Quiroz-Baez R, Friedland RP. Microbiota and Aging. A Review and Commentary. Arch Med Res 2017; 48:681-689. [PMID: 29229199 DOI: 10.1016/j.arcmed.2017.11.005] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 11/15/2017] [Indexed: 12/18/2022]
Abstract
Although there is a consensus that the dominant species that make up the adult microbiota remains unchanged in elderly people, it has been reported that there are significant alterations in the proportion and composition of the different taxa, leading to reduced microbiota diversity, as well as an increase of enteropathogens that may lead to chronic inflammation. The ageing of mucosal immune and motor systems also contributes to these changes. As the individual ages, there is a loss in the number of Peyer's patches, an altered local capacity of T and B cell functions as well as chronic macrophage activation. Also, environment, diet, place of residence and biogeography are regulatory factors of the microbiota. Communication in the gut-brain-axis is regulated by many intermediaries including diverse metabolites of the microbiota. Microbial changes have been observed in several geriatric diseases, like Parkinson's and Alzheimer's. In addition, evidence has shown that individuals with high frailty scores had a significant reduction on lactobacilli species when compared to non-frail individuals. Oral microbiota may be also especially important because of the opportunities for access to the brain through the olfactory nerve at the roof of the nose or through the abundant innervations of the oral cavity by the trigeminal and other cranial nerves. Also, there are an increasing number of reports that have suggested potential mechanisms by which the microbiota promote human health span and aging. The study of the microbiota represents an important advance in the understanding of the aging process.
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Affiliation(s)
- Carmen García-Peña
- Dirección de Investigación, Instituto Nacional de Geriatría, Ciudad de México, México
| | | | - Ricardo Quiroz-Baez
- Dirección de Investigación, Instituto Nacional de Geriatría, Ciudad de México, México
| | - Robert P Friedland
- Departament of Neurology, School of Medicine, University of Louisville, Kentucky, USA.
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Jiao L, Gan-Schreier H, Zhu X, Wei W, Tuma-Kellner S, Liebisch G, Stremmel W, Chamulitrat W. Ageing sensitized by iPLA 2β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids. Biochim Biophys Acta Mol Cell Biol Lipids 2017; 1862:1520-1533. [PMID: 28888832 DOI: 10.1016/j.bbalip.2017.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 08/28/2017] [Accepted: 09/05/2017] [Indexed: 01/06/2023]
Abstract
Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA2β is a homeostatic PLA2 by playing a role in phospholipid metabolism and remodeling. Global iPLA2β-/- mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA2β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA2β-/- mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA2β-/-mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA2β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA2β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner.
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Affiliation(s)
- Li Jiao
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany; Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China
| | - Hongying Gan-Schreier
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany
| | - Xingya Zhu
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany
| | - Wang Wei
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany
| | - Sabine Tuma-Kellner
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
| | - Wolfgang Stremmel
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany
| | - Walee Chamulitrat
- Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany.
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13
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Mastropasqua R, Agnifili L, Fasanella V, Nubile M, Gnama AA, Falconio G, Perri P, Di Staso S, Mariotti C. The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2017; 23:697-707. [PMID: 28480834 DOI: 10.1017/s1431927617000538] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.
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Affiliation(s)
| | - Luca Agnifili
- 2Ophthalmology Clinic,Department of Medicine and Aging Science,University G. d'Annunzio of Chieti-Pescara,Chieti 66100,Italy
| | - Vincenzo Fasanella
- 2Ophthalmology Clinic,Department of Medicine and Aging Science,University G. d'Annunzio of Chieti-Pescara,Chieti 66100,Italy
| | - Mario Nubile
- 2Ophthalmology Clinic,Department of Medicine and Aging Science,University G. d'Annunzio of Chieti-Pescara,Chieti 66100,Italy
| | - Agbeanda A Gnama
- 2Ophthalmology Clinic,Department of Medicine and Aging Science,University G. d'Annunzio of Chieti-Pescara,Chieti 66100,Italy
| | - Gennaro Falconio
- 2Ophthalmology Clinic,Department of Medicine and Aging Science,University G. d'Annunzio of Chieti-Pescara,Chieti 66100,Italy
| | - Paolo Perri
- 3Department of Biomedical and Surgical Sciences,Division of Ophthalmology,University of Ferrara,Ferrara 44100,Italy
| | - Silvio Di Staso
- 4Department of Surgical Science,Ophthalmic Clinic,University of L'Aquila,L'Aquila 67100,Italy
| | - Cesare Mariotti
- 5Eye Clinic,Polytechnic University of Marche,Ancona 60020,Italy
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14
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Carvalho RD, Breyner N, Menezes-Garcia Z, Rodrigues NM, Lemos L, Maioli TU, da Gloria Souza D, Carmona D, de Faria AMC, Langella P, Chatel JM, Bermúdez-Humarán LG, Figueiredo HCP, Azevedo V, de Azevedo MS. Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis. Microb Cell Fact 2017; 16:27. [PMID: 28193209 PMCID: PMC5307810 DOI: 10.1186/s12934-017-0624-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 01/03/2017] [Indexed: 12/22/2022] Open
Abstract
Background Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes. Indeed, it was demonstrated that a recombinant strain of Lactococcus lactis expressing human PAP (LL-PAP) could prevent and improve murine DNBS-induced colitis, an inflammatory bowel disease (IBD) that causes severe inflammation of the colon. Hence, in this study we sought to evaluate the protective effects of LL-PAP on 5-FU-induced experimental mucositis in BALB/c mice as a novel approach to treat the disease. Results Our results show that non-recombinant L. lactis NZ9000 have antagonistic activity, in vitro, against the enteroinvasive gastrointestinal pathogen L. monocytogenes and confirmed PAP inhibitory effect against Opportunistic E. faecalis. Moreover, L. lactis was able to prevent histological damage, reduce neutrophil and eosinophil infiltration and secretory Immunoglobulin-A in mice injected with 5-FU. Recombinant lactococci carrying antimicrobial PAP did not improve those markers of inflammation, although its expression was associated with villous architecture preservation and increased secretory granules density inside Paneth cells in response to 5-FU inflammation. Conclusions We have demonstrated for the first time that L. lactis NZ9000 by itself, is able to prevent 5-FU-induced intestinal inflammation in BALB/c mice. Moreover, PAP delivered by recombinant L. lactis strain showed additional protective effects in mice epithelium, revealing to be a promising strategy to treat intestinal mucositis.
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Affiliation(s)
- Rodrigo D Carvalho
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Natalia Breyner
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France
| | - Zelia Menezes-Garcia
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Nubia M Rodrigues
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Luisa Lemos
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Tatiane U Maioli
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Danielle da Gloria Souza
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil.,Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France
| | - Denise Carmona
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Ana M C de Faria
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Philippe Langella
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France
| | - Jean-Marc Chatel
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France
| | - Luis G Bermúdez-Humarán
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France
| | - Henrique C P Figueiredo
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Vasco Azevedo
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil
| | - Marcela S de Azevedo
- Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil.
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15
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Collins FL, Schepper JD, Rios-Arce ND, Steury MD, Kang HJ, Mallin H, Schoenherr D, Camfield G, Chishti S, McCabe LR, Parameswaran N. Immunology of Gut-Bone Signaling. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1033:59-94. [PMID: 29101652 PMCID: PMC5749247 DOI: 10.1007/978-3-319-66653-2_5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In recent years a link between the gastrointestinal tract and bone health has started to gain significant attention. Dysbiosis of the intestinal microbiota has been linked to the pathology of a number of diseases which are associated with bone loss. In addition modulation of the intestinal microbiota with probiotic bacteria has revealed to have both beneficial local and systemic effects. In the present chapter, we discuss the intestinal and bone immune systems, explore how intestinal disease affects the immune system, and examine how these pathologic changes could adversely impact bone health.
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Affiliation(s)
- Fraser L Collins
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | | | - Naiomy Deliz Rios-Arce
- Department of Physiology, Michigan State University, East Lansing, MI, USA
- Comparative Medicine and Integrative Biology Program, East Lansing, MI, USA
| | - Michael D Steury
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | - Ho Jun Kang
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | - Heather Mallin
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | - Daniel Schoenherr
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | - Glen Camfield
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | - Saima Chishti
- Department of Physiology, Michigan State University, East Lansing, MI, USA
| | - Laura R McCabe
- Department of Physiology and Department of Radiology, Biomedical Imaging Research Centre, Michigan State University, East Lansing, MI, USA.
| | - Narayanan Parameswaran
- Department of Physiology, Michigan State University, East Lansing, MI, USA.
- Comparative Medicine and Integrative Biology Program, East Lansing, MI, USA.
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16
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The Distribution of SIgA and IgG Antibody-Secreting Cells in the Small Intestine of Bactrian Camels (Camelus bactrianus) of Different Ages. PLoS One 2016; 11:e0156635. [PMID: 27249417 PMCID: PMC4889134 DOI: 10.1371/journal.pone.0156635] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 05/17/2016] [Indexed: 12/12/2022] Open
Abstract
Secretory immunoglobulin A (SIgA) and immunoglobulin G (IgG) antibody-secreting cells (ASCs) are two important cell types in the mucosal immune system. This study aimed to explore the distribution of these ASC populations in the small intestine of Bactrian camels of different ages. Twenty-four Alashan Bactrian camels were divided into the following four age groups: young (1–2 years), pubertal (3–5 years), middle-aged (6–16 years) and old (17–20 years). SIgA and IgG ASCs in the intestinal mucosa lamina propria (LP) were observed and analyzed using immunohistochemcal techniques. The results from all age groups show that both SIgA and IgG ASCs were diffusely distributed in the intestinal LP, and some cells aggregated around the crypts. Moreover, the densities of the two ASC populations gradually increased from the duodenum to the jejunum and then decreased in the ileum. Meanwhile, there were more SIgA ASCs than IgG ASCs in the duodenum, jejunum, and ileum, and these differences were significant in the young and pubertal groups (P<0.05). In addition, the SIgA and IgG ASC densities increased from the young to the pubertal period, peaked at puberty, and then gradually decreased with age. The results demonstrate that the SIgA and IgG ASC distributions help to form two immunoglobulin barriers in the intestinal mucosa to provide full protection, helping to maintain homeostasis. These findings also underscore the importance of researching the development and degeneration of intestinal mucosal immunity in Bactrian camels.
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17
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Didier ES, MacLean AG, Mohan M, Didier PJ, Lackner AA, Kuroda MJ. Contributions of Nonhuman Primates to Research on Aging. Vet Pathol 2016; 53:277-90. [PMID: 26869153 PMCID: PMC5027759 DOI: 10.1177/0300985815622974] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans.
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Affiliation(s)
- E S Didier
- Division of Microbiology, Tulane National Primate Research Center, Covington, LA, USA
| | - A G MacLean
- Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA
| | - M Mohan
- Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA
| | - P J Didier
- Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA
| | - A A Lackner
- Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA
| | - M J Kuroda
- Division of Immunology, Tulane National Primate Research Center, Covington, LA, USA
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18
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Campos-Rodríguez R, Godínez-Victoria M, Reyna-Garfias H, Arciniega-Martínez IM, Reséndiz-Albor AA, Abarca-Rojano E, Cruz-Hernández TR, Drago-Serrano ME. Intermittent fasting favored the resolution of Salmonella typhimurium infection in middle-aged BALB/c mice. AGE (DORDRECHT, NETHERLANDS) 2016; 38:13. [PMID: 26798034 PMCID: PMC5005893 DOI: 10.1007/s11357-016-9876-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 01/12/2016] [Indexed: 06/05/2023]
Abstract
Intermittent fasting (IF) reportedly increases resistance and intestinal IgA response to Salmonella typhimurium infection in mature mice. The aim of this study was to explore the effect of aging on the aforementioned improved immune response found with IF. Middle-aged male BALB/c mice were submitted to IF or ad libitum (AL) feeding for 40 weeks and then orally infected with S. typhimurium. Thereafter, infected animals were all fed AL (to maximize their viability) until sacrifice on day 7 or 14 post-infection. We evaluated body weight, bacterial load (in feces, Peyer's patches, spleen and liver), total and specific intestinal IgA, lamina propria IgA+ plasma cells, plasma corticosterone, and messenger RNA (mRNA) expression of α-chain, J-chain, and the polymeric immunoglobulin receptor (pIgR) in liver and intestinal mucosa. In comparison with the infected AL counterpart, the infected IF group (long-term IF followed by post-infection AL feeding) generally had lower intestinal and systemic bacterial loads as well as higher total IgA on both post-infection days. Both infected groups showed no differences in corticosterone levels, body weight, or food and caloric intake. The increase in intestinal IgA was associated with enhanced pIgR mRNA expression in the intestine (day 7) and liver. Thus, to maintain body weight and caloric intake, IF elicited metabolic signals that possibly induced the increased hepatic and intestinal pIgR mRNA expression found. The increase in IgA probably resulted from intestinal IgA transcytosis via pIgR. This IgA response along with phagocyte-induced killing of bacteria in systemic organs (not measured) may explain the resolution of the S. typhimurium infection.
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Affiliation(s)
- Rafael Campos-Rodríguez
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Marycarmen Godínez-Victoria
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Humberto Reyna-Garfias
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Ivonne Maciel Arciniega-Martínez
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Aldo Arturo Reséndiz-Albor
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Edgar Abarca-Rojano
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Teresita Rocío Cruz-Hernández
- Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México
| | - Maria Elisa Drago-Serrano
- Department of Biological Systems, Autonomous Metropolitan University Xochimilco Campus, Calzada del Hueso No 1100, Col. Villa Quietud, CP 04960, México, D.F., México.
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19
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Martelli S, Pender SLF, Larbi A. Compartmentalization of immunosenescence: a deeper look at the mucosa. Biogerontology 2015; 17:159-76. [PMID: 26689202 DOI: 10.1007/s10522-015-9628-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Accepted: 12/09/2015] [Indexed: 12/30/2022]
Abstract
Developments in medical care and living conditions led to an astonishing increase in life-span perspective and subsequently a rise in the old population. This can be seen as a success for public health policies but it also challenges society to adapt, in order to cope with the potentially overwhelming cost for the healthcare system. A fast-growing number of older people lose their ability to live independently because of diseases and disabilities, frailty or cognitive impairment. Many require long-term care, including home-based nursing, communities and hospital-based care. Immunosenescence, an age-related deterioration in immune functions, is considered a major contributory factor for the higher prevalence and severity of infectious diseases and the poor efficacy of vaccination in the elderly. When compared with systemic immunosenescence, alterations in the mucosal immune system with age are less well understood. For this reason, this area deserves more extensive and intensive research and support. In this article, we provide an overview of age-associated changes occurring in systemic immunity and discuss the distinct features of mucosal immunosenescence.
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Affiliation(s)
- Serena Martelli
- Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,Singapore Immunology Network (SIgN), Aging and Immunity Program, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
| | - Sylvia L F Pender
- Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Anis Larbi
- Singapore Immunology Network (SIgN), Aging and Immunity Program, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
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20
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Pratap UP, Sharma HR, Mohanty A, Kale P, Gopinath S, Hima L, Priyanka HP, ThyagaRajan S. Estrogen upregulates inflammatory signals through NF-κB, IFN-γ, and nitric oxide via Akt/mTOR pathway in the lymph node lymphocytes of middle-aged female rats. Int Immunopharmacol 2015; 29:591-598. [PMID: 26440402 DOI: 10.1016/j.intimp.2015.09.024] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 09/02/2015] [Accepted: 09/25/2015] [Indexed: 12/13/2022]
Abstract
The alterations in the secretion of sex steroids, especially estrogen, in females throughout reproductive life and its decline with age alters the functions of the neuroendocrine-immune network and renders them susceptible to age-related diseases and cancers. This study investigates the mechanisms of estrogen-induced alterations in cell-mediated immune and inflammatory responses in the lymphocytes from lymph nodes (axillary and inguinal) of ovariectomized (OVX) middle-aged female rats. Ovariectomized middle-aged (MA) Sprague-Dawley female rats (n=8) were implanted with 17β-estradiol (E2) 30-day release pellets (0.6 and 300μg). At the end of the treatment period, lymph nodes (axillary and inguinal) were isolated and examined for serum 17β-estradiol, lymphoproliferation, cytokine production, expression of p-Akt, p-mTOR, p-IκB-α and p-NF-κB (p50 and p65), extent of lipid peroxidation, nitric oxide (NO) production, cytochrome c oxidase activity and reactive oxygen species (ROS) production. There was an OVX-related decline in serum 17β-estradiol level, Con A-induced lymphoproliferation, p-Akt and p-mTOR expression, and cytochrome c oxidase (COX) activity. E2 supplementation increased serum 17β-estradiol level, lymphoproliferation, expression of p-Akt, p-mTOR, p-IκB-α and p-NF-κB (p50 and p65), lipid peroxidation, IFN-γ, TNF-α, ROS and NO production, while it decreased IL-6 production. E2 mediates inflammatory responses by increasing the levels of NO and TNF-α by up regulating IFN-γ and simultaneously promotes aging through the generation of free radicals as reflected by increased lipid peroxidation and ROS production in lymph nodes. These findings may have wide implications to immunity and inflammatory disorders including autoimmune diseases predominantly prevalent in females.
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Affiliation(s)
- Uday P Pratap
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Himanshu R Sharma
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Aparna Mohanty
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Prathamesh Kale
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Srinivasan Gopinath
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Lalgi Hima
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Hannah P Priyanka
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India
| | - Srinivasan ThyagaRajan
- Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
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21
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Mabbott NA, Kobayashi A, Sehgal A, Bradford BM, Pattison M, Donaldson DS. Aging and the mucosal immune system in the intestine. Biogerontology 2015; 16:133-45. [PMID: 24705962 DOI: 10.1007/s10522-014-9498-z] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 03/24/2014] [Indexed: 02/07/2023]
Abstract
Bacterial and viral infections of the gastrointestinal tract are more common in the elderly and represent a major cause of morbidity and mortality. The mucosal immune system provides the first line of defence against pathogens acquired by ingestion and inhalation, but its function is adversely affected in the elderly. This aging-related decline in the immune function is termed immunosenescence and is associated with diminished abilities to generate protective immunity, reduced vaccine efficacy, increased incidence of cancer, inflammation and autoimmunity, and the impaired ability to generate tolerance to harmless antigens. In this review we describe our current understanding of the effects immunosenescence has on the innate and adaptive arms of the mucosal immune system in the intestine. Current estimates suggest that by the year 2050 up to 40% of the UK population will be over 65 years old, bringing with it important health challenges. A thorough understanding of the mechanisms that contribute to the development of immunosenescence is therefore crucial to help identify novel approaches to improve mucosal immunity in the elderly.
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Affiliation(s)
- Neil A Mabbott
- The Roslin Institute & Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK,
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22
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Effect of a protein-free diet in the development of food allergy and oral tolerance in BALB/c mice. Br J Nutr 2015; 113:935-43. [PMID: 25759975 DOI: 10.1017/s0007114515000173] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of the present study was to investigate the effect of a protein-free diet in the induction of food allergy and oral tolerance in BALB/c mice. The experimental model used was mice that were fed, since weaning up to adulthood, a balanced diet in which all dietary proteins were replaced by amino acid diet (Aa). The absence of dietary proteins did not prevent the development of food allergy to ovalbumin (OVA) in these mice. However, Aa-fed mice produced lower levels of IgE, secretory IgA and cytokines. In addition, when compared with mice from control group, Aa-fed mice had a milder aversive reaction to the allergen measured by consumption of OVA-containing solution and weight loss during food allergy development. In addition, mice that did not have dietary proteins in their diets were less susceptible to induction of oral tolerance. One single oral administration was not enough to suppress specific serum Ig and IgG1 levels in the Aa-fed group, although it was efficient to induce suppression in the control group. The present results indicate that the stimulation by dietary proteins alters both inflammatory reactivity and regulatory immune reactivity in mice probably due to their effect in the maturation of the immune system.
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Okada K, Sadahiro S, Suzuki T, Tanaka A, Saito G, Masuda S, Haruki Y. The size of retrieved lymph nodes correlates with the number of retrieved lymph nodes and is an independent prognostic factor in patients with stage II colon cancer. Int J Colorectal Dis 2015; 30:1685-93. [PMID: 26260481 PMCID: PMC4675793 DOI: 10.1007/s00384-015-2357-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/02/2015] [Indexed: 02/04/2023]
Abstract
PURPOSE In stage II colon cancer, patients with many retrieved lymph nodes (LNs) have been reported to have better oncological outcomes. We tested the hypothesis that the greater number of retrieved LNs is related to a larger LN size. METHODS The subjects comprised 320 patients with stage II colon cancer who underwent curative resection. All operations were elective and were performed by the same surgeons. The maximum long axis and short axis diameters of LNs were measured on hematoxylin-eosin-stained specimens. RESULTS A total of 4,744 LNs were evaluated. The number of retrieved LNs was 14.8 ± 10.1 (mean ± SD). The long axis diameter was 4.8 ± 2.6 mm, with a median value of 4.3 mm, a maximum value of 20.4 mm, and a minimum value of 0.6 mm. The corresponding short axis diameters were 3.4 ± 1.7, 3.0, 15.1, and 0.5 mm, respectively. The highest correlation coefficient for the association with the number of LNs was obtained for the maximum value of the long axis diameter (0.59). Multivariate analysis revealed that age, tumor location, pathological T stage, and the maximum long axis diameter were independent prognostic factors. The number of LNs was not a significant factor. Patients with less than 12 LNs and a maximum long axis diameter of less than 10 mm had significantly poorer outcomes (p < 0.001). CONCLUSION In patients with stage II colon cancer, the maximum long axis diameter of LNs correlated with the number of LNs and was an independent prognostic factor.
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Affiliation(s)
- Kazutake Okada
- />Department of Surgery, Tokai University, 143 Shimokasuya Isehara, Kanagawa, 259-1193 Japan
| | - Sotaro Sadahiro
- />Department of Surgery, Tokai University, 143 Shimokasuya Isehara, Kanagawa, 259-1193 Japan
| | - Toshiyuki Suzuki
- />Department of Surgery, Tokai University, 143 Shimokasuya Isehara, Kanagawa, 259-1193 Japan
| | - Akira Tanaka
- />Department of Surgery, Tokai University, 143 Shimokasuya Isehara, Kanagawa, 259-1193 Japan
| | - Gota Saito
- />Department of Surgery, Tokai University, 143 Shimokasuya Isehara, Kanagawa, 259-1193 Japan
| | - Shinobu Masuda
- />Department of Pathology, Nihon University, Tokyo, Japan
| | - Yasuo Haruki
- />Department of Basic Medical Science, Tokai University, Isehara, Japan
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Yoshikura H. Analysis of HIV/AIDS epidemiology in Japan from 1985-2011-infection detection pattern for male homosexuals different from that for male heterosexuals but similar to that for females. Jpn J Infect Dis 2014; 68:98-105. [PMID: 25420648 DOI: 10.7883/yoken.jjid.2014.039] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
This article reviews Japanese HIV/AIDS surveillance data from 1985 to 2011. It revealed that heterosexual males are more prone to be detected as "AIDS cases," whereas male homosexuals and females are more prone to be detected as "HIV cases," irrespective of the gender, age, infection route, residential area, and nationality. The probability of being detected as an "AIDS case" increased with advanced age, irrespective of the gender and infection route. Interpretation of the data requires further information on the clinical latency of AIDS that could differ depending on differences in infection routes, gender, age, nature of the acute-phase syndrome and factors enhancing it, e.g., route and dose of infection, and mucosal immunity involved in sexually transmitted HIV/AIDS infection and the influence of age and gender on it.
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Saffrey MJ. Aging of the mammalian gastrointestinal tract: a complex organ system. AGE (DORDRECHT, NETHERLANDS) 2014; 36:9603. [PMID: 24352567 PMCID: PMC4082571 DOI: 10.1007/s11357-013-9603-2] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Accepted: 11/25/2013] [Indexed: 05/23/2023]
Abstract
Gastrointestinal disorders are a major cause of morbidity in the elderly population. The gastrointestinal tract is the most complex organ system; its diverse cells perform a range of functions essential to life, not only secretion, digestion, absorption and excretion, but also, very importantly, defence. The gastrointestinal tract acts not only as a barrier to harmful materials and pathogens but also contains the vast number of beneficial bacterial populations that make up the microbiota. Communication between the cells of the gastrointestinal tract and the central nervous and endocrine systems modifies behaviour; the organisms of the microbiota also contribute to this brain-gut-enteric microbiota axis. Age-related physiological changes in the gut are not only common, but also variable, and likely to be influenced by external factors as well as intrinsic aging of the cells involved. The cellular and molecular changes exhibited by the aging gut cells also vary. Aging intestinal smooth muscle cells exhibit a number of changes in the signalling pathways that regulate contraction. There is some evidence for age-associated degeneration of neurons and glia of the enteric nervous system, although enteric neuronal losses are likely not to be nearly as extensive as previously believed. Aging enteric neurons have been shown to exhibit a senescence-associated phenotype. Epithelial stem cells exhibit increased mitochondrial mutation in aging that affects their progeny in the mucosal epithelium. Changes to the microbiota and intestinal immune system during aging are likely to contribute to wider aging of the organism and are increasingly important areas of analysis. How changes of the different cell types of the gut during aging affect the numerous cellular interactions that are essential for normal gut functions will be important areas for future aging research.
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Affiliation(s)
- M Jill Saffrey
- Department of Life Health and Chemical Sciences, Biomedical Research Network, The Open University, Milton Keynes, MK7 6AA, UK,
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Sivro A, Lajoie J, Kimani J, Jaoko W, Plummer FA, Fowke K, Ball TB. Age and menopause affect the expression of specific cytokines/chemokines in plasma and cervical lavage samples from female sex workers in Nairobi, Kenya. IMMUNITY & AGEING 2013; 10:42. [PMID: 24498919 PMCID: PMC3874757 DOI: 10.1186/1742-4933-10-42] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2013] [Accepted: 10/05/2013] [Indexed: 12/28/2022]
Abstract
Background Aging of the immune system, known as immunosenescence, is associated with profound changes in both innate and adaptive immune responses, resulting in increased susceptibility to infection and a decreased ability to respond to vaccination. The purpose of this study was to investigate the effect of age and menopause on the expression of 22 different cytokines/chemokines in both plasma and cervical lavage samples from female sex-worker cohort from Nairobi, Kenya (age range 20–65). Results Cytokine/chemokine levels were measured using a Miliplex multiplex assay (Millipore). We found that age positively correlated with MCP-1 (p = 0.0002) and IP-10 (p = 0.03) systemic cytokine expression, and that women over 50 expressed the highest levels of these cytokines, but also had elevated expression of MIG (ANOVA p = 0.0096) and MIP-3β(ANOVA p = 0.0434). We also found that IL-8 (p = 0.047) and sCD40L (p = 0.01) systemic expression negatively correlated with age. Further, MIG (p = 0.0081) and MCP-1 (p = 0.0157) were present at higher levels in post-menopausal women suggesting a potential estrogen dependant systemic regulation of these cytokines. In cervical lavage samples, age did not directly correlate with the expression of any of the tested cytokines/chemokines, however sIL-2Rα (ANOVA p = 0.0170) and IL-15 (ANOVA p = 0.0251)were significantly higher in women over 50. Menopause was shown to have a more profound effect on cytokine expression in the cervical mucosa with MIG (p = 0.0256), MIP-3α (p = 0.0245), IL-1β (p = 0.0261), IL-6 (p = 0.0462), IL-8 (p = 0.007), IP-10 (p = 0.0357) and MCP-1 (p = 0.0427) all significantly under-expressed in post-menopausal women. Conclusions This study demonstrates that aging and menopause-associated hormonal changes are associated with significant changes in systemic and mucosal cytokine/chemokine expression, which may have implications for the age-related decline in the ability to fight against infections.
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Affiliation(s)
- Aida Sivro
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Julie Lajoie
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Joshua Kimani
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.,Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - Walter Jaoko
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - Francis A Plummer
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.,National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Keith Fowke
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.,Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - T Blake Ball
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.,Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.,Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.,National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
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The functional maturation of M cells is dramatically reduced in the Peyer's patches of aged mice. Mucosal Immunol 2013; 6:1027-37. [PMID: 23360902 PMCID: PMC3747980 DOI: 10.1038/mi.2012.141] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 12/18/2012] [Indexed: 02/04/2023]
Abstract
The transcytosis of antigens across the follicle-associated epithelium (FAE) of Peyer's patches by microfold cells (M cells) is important for the induction of efficient immune responses to mucosal antigens. The mucosal immune response is compromised by ageing, but effects on M cells were unknown. We show that M-cell density in the FAE of aged mice was dramatically reduced. As a consequence, aged Peyer's patches were significantly deficient in their ability to transcytose particulate lumenal antigen across the FAE. Ageing specifically impaired the expression of Spi-B and the downstream functional maturation of M cells. Ageing also dramatically impaired C-C motif chemokine ligand 20 expression by the FAE. As a consequence, fewer B cells were attracted towards the FAE, potentially reducing their ability to promote M-cell maturation. Our study demonstrates that ageing dramatically impedes the functional maturation of M cells, revealing an important ageing-related defect in the mucosal immune system's ability to sample lumenal antigens.
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Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol 2013; 6:666-77. [PMID: 23695511 PMCID: PMC3686595 DOI: 10.1038/mi.2013.30] [Citation(s) in RCA: 469] [Impact Index Per Article: 39.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The transcytosis of antigens across the gut epithelium by microfold cells (M cells) is important for the induction of efficient immune responses to some mucosal antigens in Peyer's patches. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells. This review highlights these important advances, with particular emphasis on: the host genes which control the functional maturation of M cells; how this knowledge has led to the rapid advance in our understanding of M-cell biology in the steady state and during aging; molecules expressed on M cells which appear to be used as "immunosurveillance" receptors to sample pathogenic microorganisms in the gut; how certain pathogens appear to exploit M cells to infect the host; and finally how this knowledge has been used to specifically target antigens to M cells to attempt to improve the efficacy of mucosal vaccines.
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Abstract
Data comparing age-related alterations in faecal IgA concentrations of dogs are not available in the literature. The present study aimed to compare the faecal concentrations of IgA in puppies, mature and senior dogs. A total of twenty-four beagle dogs were used, including eight puppies (5 months old, four females and four males), eight mature (4·6 years old, eight males) and eight senior dogs (10·6 years old, three males and five females). Fresh faecal samples were collected from each dog for three consecutive days and pooled by animal. After saline extraction, IgA content was measured by ELISA. Data were analysed by one-way ANOVA, and means were compared with Tukey's test (P < 0·05). Results showed that puppies have lower faecal IgA concentrations than mature dogs (P < 0·05); senior animals presented intermediary results. The reduced faecal IgA concentration in puppies is consistent with the reduced serum and salivary IgA concentrations reported previously, suggesting a reduced mucosal immunity in this age group. Although some studies have found an increased serum IgA concentration in older dogs, this may differ from the intestinal secretion of IgA, which appears to be lower in some senior animals (four of the eight dogs studied).
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John CM, Sandrasaigaran P, Tong CK, Adam A, Ramasamy R. Immunomodulatory activity of polyphenols derived from Cassia auriculata flowers in aged rats. Cell Immunol 2011; 271:474-9. [PMID: 21924708 DOI: 10.1016/j.cellimm.2011.08.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 08/04/2011] [Accepted: 08/22/2011] [Indexed: 01/23/2023]
Abstract
The immunomodulatory activity of Cassia auriculata (CA)-derived polyphenols was tested on aged rats. Rats (24-26 months old) were given CA polyphenols supplementation at doses of 25, 50, and 100 mg/kg for 28 days. Flow cytometry analysis of CA polyphenols-treated aged rats showed increased T and B cells percentage along with enhanced proliferation of splenocytes in both resting and LPS-stimulated cells. Increased percentage of pan T cells is further supported by an elevation of CD4+, CD8+, and CD4+CD25+ regulatory cells. In terms of innate immune cell activity, CA polyphenol supplementation reduced the oxidative burst activity of neutrophils in response to PMA and Escherichia coli activation. Our results collectively show that polyphenols derived from CA boost T cell immunity by increasing the number of T cells and its sensitivity towards stimulants and decreasing ROS production by neutrophils that could potentially harm multiple biological systems in aged individuals.
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Affiliation(s)
- Cini M John
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
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Abstract
Aging represents a complex remodeling in which both innate and adaptive immunities deteriorate. Age-related changes in humoral immunity are responsible for the reduced vaccine responses observed in elderly individuals. Although T cell alterations play a significant role in age-related humoral immune changes, alterations in B cells also occur. We here provide an overview of age-related changes in B cell markers and functions. Our studies have shown that intrinsic changes in B cells with age contribute to reduced antibody responses such as those to the influenza vaccine.
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McDonald KG, Leach MR, Huang C, Wang C, Newberry RD. Aging impacts isolated lymphoid follicle development and function. IMMUNITY & AGEING 2011; 8:1. [PMID: 21214915 PMCID: PMC3023758 DOI: 10.1186/1742-4933-8-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Accepted: 01/07/2011] [Indexed: 01/19/2023]
Abstract
BACKGROUND Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice. RESULTS We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8αα+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice. CONCLUSIONS Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence.
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Affiliation(s)
- Keely G McDonald
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
| | - Matthew R Leach
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
| | - Conway Huang
- University of Texas Southwestern Medical School, Austin Texas, 78701, USA
| | - Caihong Wang
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
| | - Rodney D Newberry
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
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Age-associated alterations in sympathetic noradrenergic innervation of primary and secondary lymphoid organs in female Fischer 344 rats. J Neuroimmunol 2010; 233:54-64. [PMID: 21186063 DOI: 10.1016/j.jneuroim.2010.11.012] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2010] [Revised: 09/24/2010] [Accepted: 11/28/2010] [Indexed: 11/21/2022]
Abstract
Normal aging processes, as well as, psychological stress affect the immune system; each can act alone, or interact with each other, to cause dysregulation of immune function substantially altering physical and mental health. The sympathetic nervous system (SNS), a major mediator of stress effects on immune function, is significantly affected by normal aging process, and stress can affect aging of the SNS. Previously, we have shown age-associated changes in sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents that affect immune regulation. The purpose of this study was to investigate sympathetic innervation of lymphoid organs and associated alterations in immune responses in young and aging female Fischer 344 (F344) rats. Histofluorescence and immunocytochemistry for NA innervation, and neurochemistry for norepinephrine (NE) levels were performed in the thymus, spleen, and mesenteric lymph nodes (MLN) isolated from 3-month-old young (normal estrous cycle), 8- to 9-month-old (onset of irregular estrous cycling), and 24-25 month, and 30-31 month female F344 rats (acyclic) at diestrus based on vaginal smears. Age-related alterations in natural killer (NK) cell activity, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production, T and B lymphocyte proliferation were examined in splenocytes. Sympathetic NA innervation and NE levels increased with aging in the thymus, declined in spleen and MLN, and was accompanied by significant reductions in NK cell activity, IL-2 and IFN-γ production, and T and B cell proliferation in old female rats. In 8-9 mo rats, NE levels in the hilar region of the spleen and IFN-γ production were unaltered, while NE levels in the end region of the spleen and IL-2 production were reduced. Collectively, these results suggest that aging is characterized by significant alterations in sympathetic NA innervation in the thymus, spleen, and MLN associated with immunosuppression, and that there is a marked shift in NA activity and immune reactivity occurring during middle-aged female rats.
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Marsilio S, Kleinschmidt S, Harder J, Nolte I, Hewicker-Trautwein M. Numbers and distribution of immune cells in the tunica mucosa of the small and large intestine of full-thickness biopsies from healthy pet cats. Anat Histol Embryol 2010; 40:61-7. [PMID: 21029151 DOI: 10.1111/j.1439-0264.2010.01039.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In this study, CD3(+) T lymphocytes and IgA(+) , IgG(+) and IgM(+) plasma cells were quantified in the tunica mucosa of the intestinal tract of 12 pet cats without gastrointestinal diseases. The study included full-thickness biopsies of the duodenum, jejunum, ileum and colon. The distribution and quantification of CD3(+) T cells, IgA(+) , IgG(+) and IgM(+) plasma cells within the intestinal tunica mucosa was performed by using immunohistochemical methods and computer-aided morphometry. CD3(+) T cells were significantly prominent in the villi and their numbers increased from duodenum to ileum but decreased towards the colon. The predominant type of plasma cells was IgA(+) cells, followed by IgM(+) cells. The number of IgG(+) cells was generally low compared to the other plasma cell types investigated. The results of the vertical distribution showed that IgA(+) and IgM(+) plasma cells were most numerous in the lower crypt areas, whilst IgG(+) plasma cells accumulated in the upper crypt region with a decline towards the villi and the lower crypt areas of control cats. All types of plasma cells showed a general decline from the duodenum towards the caudal sections of the intestinal tract regarding the horizontal distribution of plasma cells. This study provides a comprehensive overview on the vertical and horizontal distribution and the number of CD3(+) T cells and IgA(+) , IgG(+) and IgM(+) plasma cells in the intestinal tunica mucosa of pet cats.
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Affiliation(s)
- S Marsilio
- Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany
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Crooks CV, Cross ML, Wall CR. Age-related differences in integrin expression in peripheral blood lymphocytes. IMMUNITY & AGEING 2010; 7:5. [PMID: 20420705 PMCID: PMC2873253 DOI: 10.1186/1742-4933-7-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Accepted: 04/26/2010] [Indexed: 01/20/2023]
Abstract
Alpha integrins play an important role in cell to cell and cell to extra-cellular matrix interactions required for an effective T-lymphocyte-mediated immune response, however little is known about age related differences in expression of alpha integrins on T-cells in humans. We here measured alpha-4 (α4) integrin (CD49d) expression on T-lymphocytes via peripheral blood sampling, comparing parameters between cohorts of young and old adults. No age-related differences were found for the absolute numbers of T-cells, although the percentage of CD4+ T-cells in older adults was significantly greater and the percentage of CD8+ T-cells lower than in younger cohorts. Percentage and absolute numbers of CD3+ T-cells co-expressing CD49d were significantly lower in older adults compared to younger cohorts, and the percentage of gated CD4+ and CD8+ cells that co-labelled positively for CD49d was also reduced in this group. There were no age-related differences in circulating levels of cytokines (Type I interferons) that are known to regulate cell surface integrin expression. Reduced expression of alpha integrins on T-cells may be an early indicator of the loss of homeostatic control that occurs with ageing, contributing to diminished effector T-cell responses during senescence.
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Affiliation(s)
- Christine V Crooks
- Institute Food, Nutrition and Human Health, Massey University, Auckland, New Zealand.
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36
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Ogra PL. Ageing and its possible impact on mucosal immune responses. Ageing Res Rev 2010; 9:101-6. [PMID: 19664726 DOI: 10.1016/j.arr.2009.07.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2009] [Revised: 07/22/2009] [Accepted: 07/23/2009] [Indexed: 01/07/2023]
Abstract
The development, structural diversification, and functional maturation of mammalian immunologic repertoire at mucosal surfaces and the systemic lymphoid tissue is a remarkably dynamic and continuous process, which begins in early fetal life and eventually culminates in variable degree of senescence or cellular death with advancing age. This brief overview will highlight the status of our current understanding of the ontogeny of mucosal immunologic response. The role of mucosal microflora and other environmental macromolecules in the regulation of mucosal immunity relative to the process of ageing will also be reviewed.
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Hayashi O, Katayanagi Y, Ishii K, Kato T. Flow cytometric analysis of age-related changes in intestine intraepithelial lymphocyte subsets and their functional preservation after feeding mice on spirulina. J Med Food 2010; 12:982-9. [PMID: 19857060 DOI: 10.1089/jmf.2008.1260] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
We investigated age-related changes in intestinal intraepithelial lymphocyte (IEL) subsets in mice by flow cytometric analysis and their functional preservation as affected by feeding Spirulina, a cyanobacterium that is known to possess various therapeutic effects, including immune modulation activity. The number of cells possessing the leukocyte-common antigen CD45(+) cells in mice (43 weeks old) of the aged group, used as a representative marker for IELs, was significantly lower than that of adult mice (5 weeks old). Either the proportion or the number of CD45(+)CD8(+) cells of the aged mice was significantly lower than that of adult mice, corresponding to previous reports. Proportions and numbers of CD4(+)CD8(+) cells in aged mice, on the other hand, were higher than those in adult mice. Increased or decreased levels of the cell surface antigens observed in the aged mice tended to be restored in aged mice fed Spirulina (aged-SP group), which ingested a hot water extract of Spirulina (SpHW). In fact, the proportions of CD45(+)CD8(+) cells and CD45(+)TCRgammadelta(+) cells in the aged-SP group significantly increased in comparison to the control aged group, which ingested ordinary chow and water ad libitum. These results suggest that ingestion of SpHW in the aged-SP group may contribute to the functional preservation of the intestinal epithelium as a first line of mucosal barrier against infectious agents through retaining the number of certain IELs. Changes in the number of other IEL subsets and blood cells are also discussed.
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Affiliation(s)
- Osamu Hayashi
- Department of Health and Nutrition, Kagawa Nutrition University, Chiyoda, Sakado, Japan.
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Kijima Y, Iwatsuki S, Akamatsu H, Terato K, Kuwabara Y, Ueda S, Shionoya H. Natural Antibodies to Pathogenic Bacteria and their Toxins in Whey Protein Concentrate. J JPN SOC FOOD SCI 2009. [DOI: 10.3136/nskkk.56.475] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Edler D, Öhrling K, Hallström M, Karlberg M, Ragnhammar P. The number of analyzed lymph nodes - a prognostic factor in colorectal cancer. Acta Oncol 2008; 46:975-81. [PMID: 17917828 DOI: 10.1080/02841860701203537] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The prognostic significance of the number of lymph nodes examined in surgical specimen of colorectal cancer was determined. One thousand and twenty five patients with colorectal cancer stage II and III were included in the study. These patients underwent surgery from 1991 to 1997 and were enrolled in clinical trials to evaluate the efficacy of adjuvant 5-fluorouracil (5FU) based chemotherapy. The median number of examined lymph nodes was five. Only 13% of the patients had > or = 12 lymph nodes analyzed. The number of examined lymph nodes was an independent prognostic factor for overall survival in the entire group of patients with stage II and III colorectal cancer (p=0.009). Patients with a higher number of lymph nodes examined had a longer overall survival. In stage III colorectal cancer the ratio of the number of metastatic lymph nodes to the number of examined lymph nodes (lymph node ratio, LNR) was an independent prognostic factor for overall survival. A decreasing LNR was correlated with a longer overall survival (p<0.0001). Increasing age was associated with a reduction of lymph node harvest (p=0.04). Patients with rectal cancer treated with preoperative radiotherapy had a lower number of lymph nodes analyzed compared with non-radiated (p<0.001). The number of examined lymph nodes in the surgical specimen is an independent prognostic factor for overall survival in colorectal cancer. The LNR is an independent prognostic factor in stage III colorectal cancer.
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Kleinschmidt S, Meneses F, Nolte I, Hewicker-Trautwein M. Distribution of mast cell subtypes and immune cell populations in canine intestines: Evidence for age-related decline in T cells and macrophages and increase of IgA-positive plasma cells. Res Vet Sci 2008; 84:41-8. [PMID: 17521688 DOI: 10.1016/j.rvsc.2007.03.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2006] [Revised: 02/15/2007] [Accepted: 03/17/2007] [Indexed: 12/26/2022]
Abstract
The distribution and numbers of leucocytes and mast cells (MC) in the canine gastrointestinal tract of three different age groups was investigated immunhistochemically. In all age groups, CD3+ T cells were more prominent in the villus region than in the crypt areas without differences between intestinal segments, whereas macrophages were more randomly distributed. Kresylecht-violet and tryptase-positive MC were prominent in pericrypt regions with statistic significances. Chymase-bearing mast cells, IgA-, IgG- and IgM-containing cells did not show significant differences in their distribution but, except for IgG-positive cells, subjective trends with increasing numbers towards the crypts exist. The reasons for the distribution of T cells, macrophages, immunoglobulin-containing cells and mast cells are not clear. Lamina propria CD3+ T cells and macrophages significantly decreased whilst a significant increase of IgA-containing plasma cells with increasing age was found. For mast cell subtypes, IgG- and IgM-containing cells no significant changes in numbers with increasing age exist.
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Affiliation(s)
- Sven Kleinschmidt
- Department of Pathology, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany
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Yom HW, Seo JW. Gastric mucosal immune response of Helicobacter pylori-infected children. KOREAN JOURNAL OF PEDIATRICS 2008. [DOI: 10.3345/kjp.2008.51.5.492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Hye Won Yom
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
| | - Jeong Wan Seo
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
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Hall KE, Proctor DD, Fisher L, Rose S. American gastroenterological association future trends committee report: effects of aging of the population on gastroenterology practice, education, and research. Gastroenterology 2005; 129:1305-38. [PMID: 16230084 DOI: 10.1053/j.gastro.2005.06.013] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Karen E Hall
- Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, Ann Arbor, Michigan, USA
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Abstract
Gastrointestinal associated lymphoid tissue can be divided into loosely organized effector sites, which include the lamina propria and intraepithelial lymphocytes, and more organized structures, such as mesenteric lymph nodes (LNs), Peyer's patches (PPs), isolated lymphoid follicles, and cryptopatches (CPs). These organized structures in the gastrointestinal tract have been hypothesized to play the role of primary lymphoid organ, supporting the extrathymic development of T lymphocytes (CPs), secondary lymphoid organs involved in the induction of the mucosal immune response (PPs), and tertiary lymphoid structures whose function is still under debate (isolated lymphoid follicles). The most widely studied lymphoid structure found in the small intestine is the PP. PPs are secondary lymphoid structures, and their development and function have been extensively investigated. However, single lymphoid aggregates resembling PPs have been also described in humans and in the murine small intestines. These isolated lymphoid follicles have both germinal centers and an overlying follicle-associated epithelium, suggesting that they also can function as inductive sites for the mucosal immune response. This review compares and contrasts the development and function of the four main organized gastrointestinal lymphoid tissues: CPs, isolated lymphoid follicles, PPs, and mesenteric LNs.
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Affiliation(s)
- Rodney D Newberry
- Department of Internal Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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Abstract
AIM: To observe the relationship between intestinal lumen colonization with Candida albicans and mucosal secretory IgA (sIgA).
METHODS: A total of 82 specific-pathogen-free mice were divided randomly into control and colonization groups. After Candida albicans were inoculated into specific-pathogen-free mice, the number of Candida albicans adhering to cecum and mucosal membrane was counted. The lymphocyte proliferation in Peyer’s patch and in lamina propria was shown by BrdU incorporation, while mucosal sIgA (surface membrane) isotype switch in Peyer’s patch was investigated. IgA plasma cells in lamina propria were observed by immunohistochemical staining. Specific IgA antibodies to Candida albicans were measured with ELISA.
RESULTS: From d 3 to d 14 after Candida albicans gavaging to mice, the number of Candida albicans colonizing in lumen and adhering to mucosal membrane was sharply reduced. Candida albicans translocation to mesenteric lymph nodes occurred at early time points following gavage administration and disappeared at later time points. Meanwhile, the content of specific IgA was increased obviously. Proliferation and differentiation of lymphocytes in lamina propria were also increased.
CONCLUSION: Lymphocytes in lamina propria play an important role in intestinal mucosal immunity of specific-pathogen-free mice when they are first inoculated with Candida albicans. The decreasing number of Candida albicans in intestine is related to the increased level of specific IgA antibodies in the intestinal mucus.
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Affiliation(s)
- Xiao-Dong Bai
- Department of Burn Surgery, General Hospital of Armed Police Force, 69 Yong Ding Road, Hai Dian District, Beijing 100039, China.
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