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      Gut Microbiota Modulation on Intestinal Mucosal Adaptive Immunity

      review-article
      1 , , 2 , 3 ,
      Journal of Immunology Research
      Hindawi

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          Abstract

          The mammalian intestine harbors a remarkable number of microbes and their components and metabolites, which are fundamental for the instigation and development of the host immune system. The intestinal innate and adaptive immunity coordinate and interact with the symbionts contributing to the intestinal homeostasis through establishment of a mutually beneficial relationship by tolerating to symbiotic microbiota and retaining the ability to exert proinflammatory response towards invasive pathogens. Imbalance between the intestinal immune system and commensal organisms disrupts the intestinal microbiological homeostasis, leading to microbiota dysbiosis, compromised integrity of the intestinal barrier, and proinflammatory immune responses towards symbionts. This, in turn, exacerbates the degree of the imbalance. Intestinal adaptive immunity plays a critical role in maintaining immune tolerance towards symbionts and the integrity of intestinal barrier, while the innate immune system regulates the adaptive immune responses to intestinal commensal bacteria. In this review, we will summarize recent findings on the effects and mechanisms of gut microbiota on intestinal adaptive immunity and the plasticity of several immune cells under diverse microenvironmental settings.

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          Most cited references74

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          Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

          Specific members of the intestinal microbiota dramatically affect inflammatory bowel disease (IBD) in mice. In humans, however, identifying bacteria that preferentially affect disease susceptibility and severity remains a major challenge. Here, we used flow-cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the intestinal microbiota with immunoglobulin A (IgA-SEQ) and show that high IgA coating uniquely identifies colitogenic intestinal bacteria in a mouse model of microbiota-driven colitis. We then used IgA-SEQ and extensive anaerobic culturing of fecal bacteria from IBD patients to create personalized disease-associated gut microbiota culture collections with predefined levels of IgA coating. Using these collections, we found that intestinal bacteria selected on the basis of high coating with IgA conferred dramatic susceptibility to colitis in germ-free mice. Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development. Copyright © 2014 Elsevier Inc. All rights reserved.
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            A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

            There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
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              Lactobacillus reuteri induces gut intraepithelial CD4 + CD8αα + T cells

              The small intestine contains CD4+CD8αα+ double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4+ T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri. This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells. L. reuteri did not shape DP–IEL–TCR repertoire, but generated indole derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4+ T cells, allowing ThPOK downregulation and differentiation into DP IELs. Thus, L. reuteri together with a tryptophan-rich diet can reprogram intraepithelial CD4+ T cells into immunoregulatory T cells.
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                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2019
                3 October 2019
                : 2019
                : 4735040
                Affiliations
                1Hepatology Department, Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai 264001, China
                2Institute of Processing Engineering, University of Chinese Academy of Sciences, 1 North 2nd Street, Zhongguancun, Haidian District, Beijing 100049, China
                3Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, 17 Chunhui Road, Laishan District, Yantai 264003, China
                Author notes

                Guest Editor: Minggang Zhang

                Author information
                https://orcid.org/0000-0003-0195-4255
                https://orcid.org/0000-0003-3151-6889
                Article
                10.1155/2019/4735040
                6794961
                31687412
                58f58e50-00b5-4f30-8c9f-98676c538999
                Copyright © 2019 Li Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 May 2019
                : 5 August 2019
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2018YFD091102
                Categories
                Review Article

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