The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses

INRA, U910, Unité Ecologie et Physiologie du Système Digestif, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
Immunity (Impact Factor: 21.56). 10/2009; 31(4):677-89. DOI: 10.1016/j.immuni.2009.08.020
Source: PubMed


Microbiota-induced cytokine responses participate in gut homeostasis, but the cytokine balance at steady-state and the role of individual bacterial species in setting the balance remain elusive. Herein, systematic analysis of gnotobiotic mice indicated that colonization by a whole mouse microbiota orchestrated a broad spectrum of proinflammatory T helper 1 (Th1), Th17, and regulatory T cell responses whereas most tested complex microbiota and individual bacteria failed to efficiently stimulate intestinal T cell responses. This function appeared the prerogative of a restricted number of bacteria, the prototype of which is the segmented filamentous bacterium, a nonculturable Clostridia-related species, which could largely recapitulate the coordinated maturation of T cell responses induced by the whole mouse microbiota. This bacterium, already known as a potent inducer of mucosal IgA, likely plays a unique role in the postnatal maturation of gut immune functions. Changes in the infant flora may thus influence the development of host immune responses.

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    • "It is identified that segmented filamentous bacteria (SFB), a nonculturable Clostridia-related species , is showed the biggest difference between Th17 celldeficient and Th17 cell-sufficient mice, which is capable of specifically inducing Th17 cells in the gut [99] [100]. This bacterium is also known as a potent inducer of mucosal IgA, which plays a unique role during the postnatal maturation of gut immune functions [101] "

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    • "Data from GF mouse studies must also be interpreted in context as several normal host physiologic parameters are altered in these mice. For example, GF mice have underdeveloped immune systems (Atarashi et al. 2011; Gaboriau-Routhiau et al. 2009; Helgeland et al. 1996; Ivanov et al. 2009; Macpherson and Harris 2004; Umesaki et al. 1993), slower intestinal epithelial turnover (Savage et al. 1981), differences in epithelial gene expression (Chowdhury et al. 2007; Hooper et al. 2001), differing nutritional requirements, less body fat despite increased consumption (Backhed et al. 2004), and markedly enlarged ceca. The latter may lead to death from volvulus or may indirectly lower reproductive performance, presumably due to competition for space with the gravid uterus. "
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    ABSTRACT: Eukaryotic organisms are colonized by rich and dynamic communities of microbes, both internally (e.g., in the gastrointestinal and respiratory tracts) and externally (e.g., on skin and external mucosal surfaces). The vast majority of bacterial microbes reside in the lower gastrointestinal (GI) tract, and it is estimated that the gut of a healthy human is home to some 100 trillion bacteria, roughly an order of magnitude greater than the number of host somatic cells. The development of culture-independent methods to characterize the gut microbiota (GM) has spurred a renewed interest in its role in host health and disease. Indeed, associations have been identified between various changes in the composition of the GM and an extensive list of diseases, both enteric and systemic. Animal models provide a means whereby causal relationships between characteristic differences in the GM and diseases or conditions can be formally tested using genetically identical animals in highly controlled environments. Clearly, the GM and its interactions with the host and myriad environmental factors are exceedingly complex, and it is rare that a single microbial taxon associates with, much less causes, a phenotype with perfect sensitivity and specificity. Moreover, while the exact numbers are the subject of debate, it is well recognized that only a minority of gut bacteria can be successfully cultured ex vivo. Thus, to perform studies investigating causal roles of the GM in animal model phenotypes, researchers need clever techniques to experimentally manipulate the GM of animals, and several ingenious methods of doing so have been developed, each providing its own type of information and with its own set of advantages and drawbacks. The current review will focus on the various means of experimentally manipulating the GM of research animals, drawing attention to the factors that would aid a researcher in selecting an experimental approach, and with an emphasis on mice and rats, the primary model species used to evaluate the contribution of the GM to a disease phenotype. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email:
    Full-text · Article · Aug 2015 · ILAR journal / National Research Council, Institute of Laboratory Animal Resources
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    • "mechanism by which CD103 + CD11b + DCs may support intestinal Th17 cell development is through their enhanced ability to produce IL- 6 in response to microbial signals (Fig. 2a,b). Indeed, a commensal microbe that is unique in its ability to preferentially induce Th17 cells is segmented filamentous bacteria (SFB; Fig. 3) (Ivanov et al., 2009; Gaboriau-Routhiau et al., 2009). This SFB-driven Th17 development in the intestine is dependent on MHC class II expression on CD11c + cells but independent of SLOs—suggesting that intestinal DCs may provide antigenic stimulation of naïve CD4+ T cells directly in situ (Goto et al., 2014; Geem et al., 2014; Lecuyer et al., 2014). "
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    ABSTRACT: The microbiota that populates the mammalian intestine consists of hundreds of trillions of bacteria that are separated from underlying immune cells by a single layer of epithelial cells. The intestinal immune system effectively tolerates components of the microbiota that provide benefit to the host while remaining poised to eliminate those that are harmful. Antigen presenting cells, especially macrophages and dendritic cells, play important roles in maintaining intestinal homeostasis via their ability to orchestrate appropriate responses to the microbiota. Paramount to elucidating intestinal macrophage- and dendritic cell-mediated functions is the ability to effectively isolate and identify these cells from a complex cellular environment. In this review, we summarize methodology for the isolation and phenotypic characterization of macrophages and DCs from the mouse intestine and discuss how this may be useful for gaining insight into the mechanisms by which mucosal immune tolerance is maintained. Copyright © 2015. Published by Elsevier B.V.
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