Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D.. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Natl Acad Sci USA 108: 11548-11553

Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2011; 108(28):11548-53. DOI: 10.1073/pnas.1108924108
Source: PubMed


Vertebrates typically harbor a rich gastrointestinal microbiota, which has coevolved with the host over millennia and is essential for several host physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T-helper cell type 17 (Th17) population in the small-intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17-dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type 1 diabetes in this prototypical, spontaneous model. There was a strong cosegregation of SFB positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T-cell compartments of the gut, pancreas, or systemic lymphoid tissues. Th17-signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4(+) T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, probably reflecting their variable dependence on different Th subsets.

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    • "SFB protect from invasion by the pathogenic microorganism Citrobacter rodentium by inducing IL-22 production by Th17 cells that inhibits the growth of this microorganism [88]. Similarly, SFB protect from development of type 1-diabetes (T1D) the nonobese diabetes (NOD) mice [89], a spontaneous model of T1D, in an IL-17-dependent manner. "
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    ABSTRACT: A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.
    Full-text · Article · Jul 2014 · Research Journal of Immunology
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    • "On the other hand, SFB protects from invasion by the pathogenic microorganism, Citrobacter rodentium, by inducing IL-22 production by Th17 cells that inhibits the growth of this microorganism [9]. Similarly, SFB protects in an IL-17-dependent manner against development of type 1 diabetes (T1D) in Non Obese Diabetes (NOD) mice [18], a spontaneous model of T1D. In this case, SFB-induced Th17 cells are not involved in disease pathogenesis , but appear to be protective through a mechanism that involves TGFb [19]. "
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    ABSTRACT: The interplay between the immune response and the gut microbiota is complex. Although it is well-established that the gut microbiota is essential for the proper development of the immune system, recent evidence indicates that the cells of the immune system also influence the composition of the gut microbiota. This interaction can have important consequences for the development of inflammatory diseases, including autoimmune diseases and allergy, and the specific mechanisms by which the gut commensals drive the development of different types of immune responses are beginning to be understood. Furthermore, sex hormones are now thought to play a novel role in this complex relationship, and collaborate with both the gut microbiota and immune system to influence the development of autoimmune disease. In this review, we will focus on recent studies that have transformed our understanding of the importance of the gut microbiota in inflammatory responses.
    Full-text · Article · Mar 2014 · FEBS letters
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    • "For example, C56BL/6 mice bred by Taconic Farms harbour more lamina propria lymphocytes than those bred by Jackson Laboratory and only caecal flora from Taconic mice is able to induce lamina propria lymphocyte formation in colonized germ-free mice [26]. Similarly, differential susceptibility to streptozotocin-induced diabetes in mice from Taconic Farms, Jackson Laboratory or Charles River Laboratories has been observed [27], [28]. Together, these findings highlight the importance of the microbiota in the development of several inflammatory or metabolic diseases and the need to keep experimental setups including housing conditions and microbiota as stable as possible to facilitate comparisons among studies performed in different animal facilities. "
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    ABSTRACT: A functional mucus layer is a key requirement for gastrointestinal health as it serves as a barrier against bacterial invasion and subsequent inflammation. Recent findings suggest that mucus composition may pose an important selection pressure on the gut microbiota and that altered mucus thickness or properties such as glycosylation lead to intestinal inflammation dependent on bacteria. Here we used TM-IEC C1galt (-/-) mice, which carry an inducible deficiency of core 1-derived O-glycans in intestinal epithelial cells, to investigate the effects of mucus glycosylation on susceptibility to intestinal inflammation, gut microbial ecology and host physiology. We found that TM-IEC C1galt (-/-) mice did not develop spontaneous colitis, but they were more susceptible to dextran sodium sulphate-induced colitis. Furthermore, loss of core 1-derived O-glycans induced inverse shifts in the abundance of the phyla Bacteroidetes and Firmicutes. We also found that mucus glycosylation impacts intestinal architecture as TM-IEC C1galt(-/-) mice had an elongated gastrointestinal tract with deeper ileal crypts, a small increase in the number of proliferative epithelial cells and thicker circular muscle layers in both the ileum and colon. Alterations in the length of the gastrointestinal tract were partly dependent on the microbiota. Thus, the mucus layer plays a role in the regulation of gut microbiota composition, balancing intestinal inflammation, and affects gut architecture.
    Full-text · Article · Jan 2014 · PLoS ONE
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