The Experts below are selected from a list of 795 Experts worldwide ranked by ideXlab platform

You Jeong Lee - One of the best experts on this subject based on the ideXlab platform.

  • Segmented Filamentous Bacteria induce divergent populations of antigen specific cd4 t cells in the small intestine
    Molecules and Cells, 2019
    Co-Authors: Jisun Jung, Daehee Han, Charles D Surh, You Jeong Lee
    Abstract:

    CD4 T cells differentiate into RORγt/IL-17A-expressing cells in the small intestine following colonization by Segmented Filamentous Bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naive precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naive CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal Bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.

  • Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine
    KOREAN SOC MOLECULAR & CELLULAR BIOLOGY, 2019
    Co-Authors: Jisun Jung, Daehee Han, Charles D Surh, You Jeong Lee
    Abstract:

    CD4 T cells differentiate into ROR gamma t/IL-17A-expressing cells in the small intestine following colonization by Segmented Filamentous Bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naive precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naive CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal Bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset. C.The Korean Society for Molecular and Cellular Biology. All rights reserved

Ivaylo I. Ivanov - One of the best experts on this subject based on the ideXlab platform.

  • induction of th17 cells by Segmented Filamentous Bacteria in the murine intestine
    Journal of Immunological Methods, 2015
    Co-Authors: Adam M Farkas, Kenya Honda, Yoshiyuki Goto, Casandra Panea, Gaku Nakato, Marta Galandiez, Seiko Narushima, Ivaylo I. Ivanov
    Abstract:

    Segmented Filamentous Bacteria (SFB) are Gram-positive, anaerobic, spore-forming commensals that reside in the gut of many animal species. Described more than forty years ago, SFB have recently gained interest due to their unique ability to modulate the host immune system through induction of IgA and Th17 cells. Here, we describe a collection of methods to detect and quantify SFB and SFB adhesion in intestinal mucosa, as well as SFB-specific CD4 T cells in the lamina propria. In addition, we describe methods for purification of SFB from fecal material of SFB-monoassociated gnotobiotic mice. Using these methods we examine the kinetics of SFB colonization and Th17 cell induction. We also show that SFB colonize unevenly the intestinal mucosa and that SFB adherence occurs predominantly in the terminal ileum and correlates with an increased proportion of SFB-specific Th17 cells.

  • Segmented Filamentous Bacteria antigens presented by intestinal dendritic cells drive mucosal th17 cell differentiation
    Immunity, 2014
    Co-Authors: Yoshiyuki Goto, Casandra Panea, Gaku Nakato, Anna Cebula, Carolyn Lee, Marta Galan Diez, Terri M Laufer, Leszek Ignatowicz, Ivaylo I. Ivanov
    Abstract:

    How commensal microbiota contributes to immune cell homeostasis at barrier surfaces is poorly understood. Lamina propria (LP) T helper 17 (Th17) cells participate in mucosal protection and are induced by commensal Segmented Filamentous Bacteria (SFB). Here we show that MHCII-dependent antigen presentation of SFB antigens by intestinal dendritic cells (DCs) is crucial for Th17 cell induction. Expression of MHCII on CD11c(+) cells was necessary and sufficient for SFB-induced Th17 cell differentiation. Most SFB-induced Th17 cells recognized SFB in an MHCII-dependent manner. SFB primed and induced Th17 cells locally in the LP and Th17 cell induction occurred normally in mice lacking secondary lymphoid organs. The importance of other innate cells was unveiled by the finding that MHCII deficiency in group 3 innate lymphoid cells (ILCs) resulted in an increase in SFB-independent Th17 cell differentiation. Our results outline the complex role of DCs and ILCs in the regulation of intestinal Th17 cell homeostasis.

  • the genome of th17 cell inducing Segmented Filamentous Bacteria reveals extensive auxotrophy and adaptations to the intestinal environment
    Cell Host & Microbe, 2011
    Co-Authors: Andrew Sczesnak, Ivaylo I. Ivanov, Nicola Segata, Xiang Qin, Dirk Gevers, Joseph F Petrosino, Curtis Huttenhower, Dan R Littman
    Abstract:

    Summary Perturbations of the composition of the symbiotic intestinal microbiota can have profound consequences for host metabolism and immunity. In mice, Segmented Filamentous Bacteria (SFB) direct the accumulation of potentially proinflammatory Th17 cells in the intestinal lamina propria. We present the genome sequence of SFB isolated from monocolonized mice, which classifies SFB phylogenetically as a unique member of Clostridiales with a highly reduced genome. Annotation analysis demonstrates that SFB depend on their environment for amino acids and essential nutrients and may utilize host and dietary glycans for carbon, nitrogen, and energy. Comparative analyses reveal that SFB are functionally related to members of the genus Clostridium and several pathogenic or commensal "minimal" genera, including Finegoldia , Mycoplasma , Borrelia , and Phytoplasma . However, SFB are functionally distinct from all 1200 examined genomes, indicating a gene complement representing biology relatively unique to their role as a gut commensal closely tied to host metabolism and immunity.

  • gut residing Segmented Filamentous Bacteria drive autoimmune arthritis via t helper 17 cells
    Immunity, 2010
    Co-Authors: Hsin Jung Wu, Ivaylo I. Ivanov, Dan R Littman, Jaime Darce, Kimie Hattori, Tatsuichiro Shima, Yoshinori Umesaki, Christophe Benoist
    Abstract:

    Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, Segmented Filamentous Bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease.

  • Segmented Filamentous Bacteria take the stage
    Mucosal Immunology, 2010
    Co-Authors: Ivaylo I. Ivanov, Dan R Littman
    Abstract:

    Commensal Bacteria are crucial for maturation and function of the mucosal immune system. However, the mechanisms of these interactions are poorly understood. In addition, the role of the composition of the microbiota and the importance of individual species in this community in stimulating different types of immunity are major unanswered questions. We recently showed that the balance between two major effector T cell populations in the intestine, IL-17+ Th17 cells and Foxp3+ Tregs, requires signals from commensal Bacteria and is dependent on the composition of the intestinal microbiota. Comparison of microbiota from Th17 cell-deficient and Th17 cell-sufficient mice identified Segmented Filamentous Bacteria (SFB) as capable of specifically inducing Th17 cells in the gut. SFB represent the first example of a commensal species that can skew the mucosal effector T cell balance and thus affect the immune fitness of the individual.

Pawan Kumar - One of the best experts on this subject based on the ideXlab platform.

  • intestinal interleukin 17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation
    Immunity, 2016
    Co-Authors: Pawan Kumar, Leticia Monin, Patricia Castillo, Waleed Elsegeiny, William Horne, Taylor Eddens, Amit Vikram, Misty Good, Alexi A Schoenborn, Kyle Bibby
    Abstract:

    Interleukin-17 (IL-17) and IL-17 receptor (IL-17R) signaling are essential for regulating mucosal host defense against many invading pathogens. Commensal Bacteria, especially Segmented Filamentous Bacteria (SFB), are a crucial factor that drives T helper 17 (Th17) cell development in the gastrointestinal tract. In this study, we demonstrate that Th17 cells controlled SFB burden. Disruption of IL-17R signaling in the enteric epithelium resulted in SFB dysbiosis due to reduced expression of α-defensins, Pigr, and Nox1. When subjected to experimental autoimmune encephalomyelitis, IL-17R-signaling-deficient mice demonstrated earlier disease onset and worsened severity that was associated with increased intestinal Csf2 expression and elevated systemic GM-CSF cytokine concentrations. Conditional deletion of IL-17R in the enteric epithelium demonstrated that there was a reciprocal relationship between the gut microbiota and enteric IL-17R signaling that controlled dysbiosis, constrained Th17 cell development, and regulated the susceptibility to autoimmune inflammation.

  • hyper th17 responses in il 17r knockout is regulated by Segmented Filamentous Bacteria sfb muc4p 857
    Journal of Immunology, 2014
    Co-Authors: Pawan Kumar, Waleed Elsegeiny, Jeremy P Mcaleer, Rachel Armentrout, Derek Pociask, Jay K Kolls
    Abstract:

    Blockade or genetic deletion of IL-17RA resulted in marked increases in IL-17 response by T-cells. We hypothesize that the hyper Th17 response in IL-17 deficient mice is due to alterations of the gut microbiome particularly overgrowth of Segmented Filamentous Bacteria (SFB). Our data shows that Il17ra-/- and Il17rc-/- mice have overgrowth of SFB (10 fold higher than WT.Taconic), suggesting a critical role of IL-17 signaling in SFB colonization. Higher SFB colonization in Il17ra-/- and Il17rc-/- mice results in expansion of IL-17A and IL-22 producing Th17 cells. As further evidence that this expansion was not T-cell intrinsic, we observed similar frequencies of IL-17 producing cells in WT and Il17ra-/- when naive T-cells were polarized in vitro to Th17 cells. Furthermore, vancomycin depletion of SFB in Il17ra-/- mice resulted into fewer Th17 cells in the lamina propria and spleen, suggesting gut microflora responsible for hyper Th17 response. SFB-colony free WT mice with intact IL-17 signaling can control SFB overgrowth but IL-17 deficient mice could not following SFB inoculation. To further define the role of IL-17 in SFB colonization, we have generated SFB-free Il17ra conditional knockout (Il17rafl/flxe2a cre) mice. SFB-free Il17rafl/flxe2a cre mice are devoid of hyper Th17 responses, and SFB inoculation resulted into acquisition of hyper Th17 phenotype as observed in Il17ra-/-. Our data suggest that IL-17 signaling regulates SFB colonization and associated Th17 responses.

Anton C. Beynen - One of the best experts on this subject based on the ideXlab platform.

  • Intestinal, Segmented, Filamentous Bacteria in a wide range of vertebrate species:
    Laboratory animals, 1993
    Co-Authors: H. L. B. M. Klaasen, J. P. Koopman, M. E. Van Den Brink, M. H. Bakker, F. G. J. Poelma, Anton C. Beynen
    Abstract:

    Segmented, Filamentous Bacteria (SFBs) form a group of Bacteria with similar morphology and are identified on the basis of their morphology only. The relationships of these organisms are unclear as the application of formal taxonomic criteria is impossible currently due to the lack of an in vitro technique to culture SFBs. The intestine of laboratory animals such as mice, rats, chickens, dogs, cats and pigs is known to harbour SFBs. To see whether this extends to other animal species, intestines from 18 vertebrate species, including man, were examined. SFBs were detected with light microscopy in the cat, dog, rhesus monkey, crab-eating macaque, domestic fowl, South African claw-footed toad, carp, man, laboratory mouse and rat, wood mouse, jackdaw and magpie. These results suggest that non-pathogenic SFBs are ubiquitous in the animal kingdom. Among apparently identical animals, there was considerable variation in the degree of SFB colonization. It is suggested that SFB colonization could serve as a criteri...

  • Apathogenic, intestinal, Segmented, Filamentous Bacteria stimulate the mucosal immune system of mice.
    Infection and immunity, 1993
    Co-Authors: H. L. B. M. Klaasen, J. P. Koopman, M. E. Van Den Brink, M. H. Bakker, F. G. J. Poelma, P.j. Van Der Heijden, W. Stok, W.m.c. Eling, Anton C. Beynen
    Abstract:

    Segmented Filamentous Bacteria (SFBs) are apathogenic autochthonous Bacteria in the murine small intestine that preferentially attach to Peyer9s patch epithelium. SFBs have never been cultured in vitro. We have studied the effects of SFBs on the immune system of the host. Mice monoassociated with SFBs were compared with germ-free mice and with mice without SFBs but with a specific-pathogen-free (SPF) gut flora. SFBs versus no microbial flora raised the number of lymphoid cells in the lamina propria of the ileal and cecal mucosa, raised the number of immunoglobulin A (IgA)-secreting cells in the intestinal mucosa, produced elevated IgA titers in serum and intestinal secretions, and enhanced the concanavalin A-induced proliferative responses of mesenteric lymph node cells. The SPF flora had effects similar to but less pronounced than those mediated by SFBs. The results indicate that SFBs stimulate the mucosal immune system to a greater extent than do other autochthonous gut Bacteria.

  • intestinal Segmented Filamentous Bacteria and colonisation resistance of mice to pathogenic Bacteria
    Microbial Ecology in Health and Disease, 1992
    Co-Authors: H. L. B. M. Klaasen, J. P. Koopman, M. E. Van Den Brink, M. H. Bakker, F. G. J. Poelma, Anton C. Beynen
    Abstract:

    We examined the possibility that Segmented, Filamentous Bacteria (FBs) in the ileum of mice play a role in host resistance to pathogens by comparing four groups of mice, namely germ-free mice, mice mono-associated with FBs, FB-free mice with a specified pathogen-free (SPF) flora, and FB-positive SPF mice, after oral administration of viable cells of either Salmonella enteritidis or Enterobacter cloacae . The SPF gut flora with or without FBs reduced colonisation of host tissues by pathogens to a similar extent. FBs alone did not reduce mean colonisation, except for salmonella counts in spleen. Mice mono associated with FBs had a lower incidence of animals with salmonella-positive livers and spleens than did germ-free mice. When compared with the germ-free status, both the SPF flora and FBs raised the serum IgA concentration irrespective of the type of pathogen challenge. The SPF flora consistently raised the concanavalin A-induced proliferative response of isolated mesenteric lymph node cells (MLNC). In MLNC from FB-positive SPF mice, the concanavalin A-induced proliferative response was lower than in FB-free SPF mice, but the salmonella antigen-induced response of spleen cells (SC) was higher; these effects were independent of the type of pathogen challenge. The in vitro proliferative response of Peyer’s patch cells to various antigens was not affected by the type of gut flora of mice challenged with either Salmonella enteritidis or Enterobacter cloacae . Keywords: Segmented Filamentous Bacteria; Colonisation resistance; Translocation; Mouse intestine; Enteropathogens; Salmonella; Enterobacter.

  • different degree of ileal colonization by Segmented Filamentous Bacteria in two strains of mice
    Journal of Experimental Animal Science, 1992
    Co-Authors: H. L. B. M. Klaasen, J. P. Koopman, M. E. Van Den Brink, M. H. Bakker, F. G. J. Poelma, B Peters, Anton C. Beynen
    Abstract:

    Segmented, Filamentous Bacteria (SFBs) are autochthonous, apathogenic inhabitants of the ileum of various animal species. Outbred Swiss (Cpb:SE) mice have significantly higher degrees of SFB colonization than do inbred BALB/c mice. The present studies were carried out to identify determinants of this strain difference. In a cross-fostering experiment it was shown that SFB colonization of the pups is determined by the strain of the pups themselves rather than by the strain of the nursing dam. Thus, maternal effects may not be involved in SFB colonization. In a cross-infecting experiment using germ-free and SFB-positive animals of the two mouse strains, it was found that ileal SFB colonization is determined by host characteristics rather than by origin of the SFBs. Thus, SFBs that are specific for a given mouse strain may not exist in the two strains of mice. It is concluded that the mouse strain difference in SFB colonization is determined by host characteristics, which probably have a genetic basis.

  • intestinal Segmented Filamentous Bacteria
    Fems Microbiology Reviews, 1992
    Co-Authors: H. L. B. M. Klaasen, J. P. Koopman, F. G. J. Poelma, Anton C. Beynen
    Abstract:

    Segmented, Filamentous Bacteria (SFBs) are autochthonous, apathogenic Bacteria, occuring in the ileum of mice and rats. Although the application of formal taxonomic criteria is imposible due to the lack of an in vitro technique to culture SFBs, microbes with a similar morphology, found in the intestine of a wide range of vertebrate and invertebrate host species, are considered to be related. SFBs are firmly attached to the epithelial cells of the distal ileal mucosa, their preferential ecological niche being the epithelium covering the Peyer's patches. Electron microscopic studies have demonstrated a considerable morphological diversity of SFBs, which may relate to different stages of a life cycle. Determinants of SFB colonization in vivo are host species, genotypical and phenotypical characteristics of the host, diet composition, environmental stress and antimicrobial drugs. SFBs can survive in vitro incubation, but do not multiply. On the basis of their apathogenic character and intimate relationship with the host, it is suggested that SFBs contribute to development and/or maintenance of host resistance to enteropathogens.

Kyle Bibby - One of the best experts on this subject based on the ideXlab platform.

  • intestinal interleukin 17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation
    Immunity, 2016
    Co-Authors: Pawan Kumar, Leticia Monin, Patricia Castillo, Waleed Elsegeiny, William Horne, Taylor Eddens, Amit Vikram, Misty Good, Alexi A Schoenborn, Kyle Bibby
    Abstract:

    Interleukin-17 (IL-17) and IL-17 receptor (IL-17R) signaling are essential for regulating mucosal host defense against many invading pathogens. Commensal Bacteria, especially Segmented Filamentous Bacteria (SFB), are a crucial factor that drives T helper 17 (Th17) cell development in the gastrointestinal tract. In this study, we demonstrate that Th17 cells controlled SFB burden. Disruption of IL-17R signaling in the enteric epithelium resulted in SFB dysbiosis due to reduced expression of α-defensins, Pigr, and Nox1. When subjected to experimental autoimmune encephalomyelitis, IL-17R-signaling-deficient mice demonstrated earlier disease onset and worsened severity that was associated with increased intestinal Csf2 expression and elevated systemic GM-CSF cytokine concentrations. Conditional deletion of IL-17R in the enteric epithelium demonstrated that there was a reciprocal relationship between the gut microbiota and enteric IL-17R signaling that controlled dysbiosis, constrained Th17 cell development, and regulated the susceptibility to autoimmune inflammation.