Interactions Between the Microbiota and the Immune System

The Howard Hughes Medical Institute and Department of Immunology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Science (Impact Factor: 33.61). 06/2012; 336(6086):1268-73. DOI: 10.1126/science.1223490
Source: PubMed


The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host-microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.

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Available from: Andrew J Macpherson, Aug 11, 2015
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    • "Reduces Activation of Th17 Cells in the Intestine Th17 cells are a pathogenic effector lineage in the EAU model, and an elevated Th17-cell-mediated response was reported to correlate with disease in uveitis patients (Chi et al., 2008; Luger et al., 2008; Wang et al., 2012). Several reports have shown the importance of gut commensal microbiota for development of Th17 cells (see Hooper et al., 2012, for review). "
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    ABSTRACT: Activated retina-specific T cells that have acquired the ability to break through the blood-retinal barrier are thought to be causally involved in autoimmune uveitis, a major cause of human blindness. It is unclear where these autoreactive T cells first become activated, given that their cognate antigens are sequestered within the immune-privileged eye. We demonstrate in a novel mouse model of spontaneous uveitis that activation of retina-specific T cells is dependent on gut commensal microbiota. Retina-specific T cell activation involved signaling through the autoreactive T cell receptor (TCR) in response to non-cognate antigen in the intestine and was independent of the endogenous retinal autoantigen. Our findings not only have implications for the etiology of human uveitis, but also raise the possibility that activation of autoreactive TCRs by commensal microbes might be a more common trigger of autoimmune diseases than is currently appreciated. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 08/2015; 43(2):343-53. DOI:10.1016/j.immuni.2015.07.014 · 21.56 Impact Factor
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    • "The gastrointestinal commensal microbiota play a critical role in shaping host immune and metabolic responses (Bä ckhed et al., 2005; Chu and Mazmanian, 2013; Lee and Mazmanian, 2010; Round and Mazmanian, 2009). Although pathogenic bacteria trigger inflammation and symbiotic bacteria promote tolerance, both sets of responses involve the activation of host pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) (Hooper et al., 2012; Palm and Medzhitov, 2009). In the case of commensal bacteria, PRR signaling in the absence of tissue damage channels the immune response toward tolerance (reviewed in Chu and Mazmanian, 2013). "
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    ABSTRACT: Commensal microbiota promote mucosal tolerance in part by engaging regulatory T (Treg) cells via Toll-like receptors (TLRs). We report that Treg-cell-specific deletion of the TLR adaptor MyD88 resulted in deficiency of intestinal Treg cells, a reciprocal increase in T helper 17 (Th17) cells and heightened interleukin-17 (IL-17)-dependent inflammation in experimental colitis. It also precipitated dysbiosis with overgrowth of segmented filamentous bacteria (SFB) and increased microbial loads in deep tissues. The Th17 cell dysregulation and bacterial dysbiosis were linked to impaired anti-microbial intestinal IgA responses, related to defective MyD88 adaptor- and Stat3 transcription factor-dependent T follicular regulatory and helper cell differentiation in the Peyer's patches. These findings establish an essential role for MyD88-dependent microbial sensing by Treg cells in enforcing mucosal tolerance and maintaining commensalism by promoting intestinal Treg cell formation and anti-commensal IgA responses. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 07/2015; 43(2). DOI:10.1016/j.immuni.2015.06.014 · 21.56 Impact Factor
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    • "Commensal bacteria living in the human gastrointestinal tract provide a biological barrier against the invasion of pathogens and contribute to the modulation of the immune system (Hooper et al., 2012; Maynard et al., 2012). Disturbance of intestinal microbiota may result in dysfunction of the mucosal barrier, as it has been shown in animal models that treatment of antibiotics altered the colonic mucus layer (Wlodarska et al., 2011), increased bacterial translocation (Wang et al., 2014), and led to intestinal sensory and motor changes (Aguilera et al., 2015). "
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    ABSTRACT: Fecal microbiota transplantation (FMT) is a promising therapy, despite some reports of adverse side effects. Bacterial consortia transplantation (BCT) for targeted restoration of the intestinal ecosystem is considered a relatively safe and simple procedure. However, no systematic research has assessed the effects of FMT and BCT on immune responses of intestinal mucosal barrier in patients. We conducted complementary studies in animal models on the effects of FMT and BCT, and provide recommendations for improving the clinical outcomes of these treatments. To establish the dysbiosis model, male BALB/c mice were treated with ceftriaxone intra-gastrically for 7 days. After that, FMT and BCT were performed on ceftriaxone-treated mice for 3 consecutive days to rebuild the intestinal ecosystem. Post-FMT and post-BCT changes of the intestinal microbial community and mucosal barrier functions were investigated and compared. Disruption of intestinal microbial homeostasis impacted the integrity of mucosal epithelial layer, resulting in increased intestinal permeability. These outcomes were accompanied by overexpression of Muc2, significant decrease of SIgA secretion, and overproduction of defensins and inflammatory cytokines. After FMT and BCT, the intestinal microbiota recovered quickly, this was associated with better reconstruction of mucosal barriers and re-establishment of immune networks compared with spontaneous recovery (SR). Although based on a short-term study, our results suggest that FMT and BCT promote the re-establishment of intestinal microbial communities in mice with antibiotic-induced dysbiosis, and contribute to the temporal and spatial interactions between microbiota and mucosal barriers. The effects of BCT are comparable to that of FMT, especially in normalizing the intestinal levels of Muc2, SIgA, and defensins.
    Frontiers in Microbiology 07/2015; 6:692. DOI:10.3389/fmicb.2015.00692 · 3.99 Impact Factor
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