The Toll-Like Receptor 2 Pathway Establishes Colonization by a Commensal of the Human Microbiota

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Science  21 Apr 2011:
DOI: 10.1126/science.1206095


Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. In 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) of B. fragilis signals through TLR2 directly on Foxp3+ regulatory T cells to promote immunologic tolerance. Remarkably, B. fragilis lacking PSA is unable to restrain T helper 17 (Th17) 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 via recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.