Round, June L. and Lee, S. Melanie and Li, Jennifer and Tran, Gloria and Jabri, Bana and Chatila, Talal A. and Mazmanian, Sarkis K. (2011) The Toll-Like Receptor 2 Pathway Establishes Colonization by a Commensal of the Human Microbiota. Science, 332 (6032). pp. 974-977. ISSN 0036-8075 http://resolver.caltech.edu/CaltechAUTHORS:20110531-120122725
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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.
|Additional Information:||© 2011 American Association for the Advancement of Science. Received 15 February 2011; accepted 6 April 2011; published online 21 April 2011. We thank S. W. McBride and Y. Shen (California Institute for Technology) for help with bacterial colonization and germ-free studies. We are grateful to A. Rudensky [Memorial Sloan-Kettering Cancer Center and Howard Hughes Medical Institute (HHMI)] for the gift of Foxp3-DTR mice and L. Hooper (University of Texas Southwestern and HHMI) for germ-free Rag1−/− mice. We thank members of the Mazmanian laboratory for their critical review of the manuscript. B.J. acknowledges support from the Crohn’s and Colitis Foundation of America (CCFA) (award 2831) and T.A.C acknowledges support from the NIH (grant AI 080002). J.L.R. is a Merck Fellow of the Jane Coffin Childs Memorial Fund. S.K.M. is a Searle Scholar. This work was supported by funding from the NIH (grants DK 078938, DK 083633, AI 088626), the Damon Runyon Cancer Research Foundation, and the CCFA (award 2405) to S.K.M. J.L.R. and S.K.M. have a patent application (PCT/US2008/082928) on the use of PSA as a therapy for inflammatory bowel disease. The authors have no competing financial interests related to this publication.|
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|Deposited By:||Jason Perez|
|Deposited On:||31 May 2011 20:20|
|Last Modified:||31 May 2011 20:20|
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