title: The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.
abstract: Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. jround@caltech.edu
authors.forename: June L
authors.initials: JL
authors.lastname: Round
authors.forename: S Melanie
authors.initials: SM
authors.lastname: Lee
authors.forename: Jennifer
authors.initials: J
authors.lastname: Li
authors.forename: Gloria
authors.initials: G
authors.lastname: Tran
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
authors.forename: Talal A
authors.initials: TA
authors.lastname: Chatila
authors.forename: Sarkis K
authors.initials: SK
authors.lastname: Mazmanian
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis / Q000254:growth & development* / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000382:microbiology; D005856:Germ-Free Life; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013559:Symbiosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*
chemical_list: D011135:Polysaccharides, Bacterial; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10