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.

Download full-text


Available from: Giovanni Brandi,
  • Source
    • "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] "

  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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:
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 08/2015; 56(2). DOI:10.1093/ilar/ilv021 · 2.39 Impact Factor
  • Source
    • "This group of segmented bacteria are found in gut microbiota of vertebrates like chickens, rodents and fish and are anchored to the gut epithelial cells in the ileum and play an important role in modulating host immune responses [25]. They increase, activate, and coordinate maturation of epithelial lymphocytes [26]–[28], and induce IgA secreting cells [29]. It was surprising to see this OTU increased only in the C. perfringens infected group when predisposing factors were not used but its abundance was not altered in the presence of C. perfringens when predisposing factors were also applied. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Clostridium perfringens causes enteric diseases in animals and humans. In poultry, avian-specific C. perfringens strains cause necrotic enteritis, an economically significant poultry disease that costs the global industry over $2 billion annually in losses and control measures. With removal of antibiotic growth promoters in some countries this disease appears to be on the rise. In experimental conditions used to study disease pathogenesis and potential control measures, reproduction of the disease relies on the use of predisposing factors such as Eimeria infection and the use of high protein diets, indicating complex mechanisms involved in the onset of necrotic enteritis. The mechanisms by which the predisposing factors contribute to disease progression are not well understood but it has been suggested that they may cause perturbations in the microbiota within the gastrointestinal tract. We inspected changes in cecal microbiota and short chain fatty acids (SCFA) induced by Eimeria and fishmeal, in birds challenged or not challenged with C. perfringens. C. perfringens challenge in the absence of predisposing factors did not cause significant changes in either the alpha or beta diversity of the microbiota nor in concentrations of SCFA. Moreover, there was no C. perfringens detected in the cecal microbiota 2 days post-challenge without the presence of predisposing factors. In contrast, both fishmeal and Eimeria caused significant changes in microbiota, seen in both alpha and beta diversity and also enabled C. perfringens to establish itself post challenge. Eimeria had its strongest influence on intestinal microbiota and SCFA when combined with fishmeal. Out of 6 SCFAs measured, including butyric acid, none were significantly influenced by C. perfringens, but their levels were strongly modified following the use of both predisposing factors. There was little overlap in the changes caused following Eimeria and fishmeal treatments, possibly indicating multiple routes for progressing towards clinical symptoms of necrotic enteritis.
    PLoS ONE 08/2014; 9(8):e104739. DOI:10.1371/journal.pone.0104739 · 3.23 Impact Factor
Show more