Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which is produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew of germ-free mice. We identify Toll-like receptors as crucial to the convergence of innate and adaptive responses stimulated by PSA. Optimization of the Th1 cytokine interferon-γ in PSA-stimulated dendritic cell–CD4+ T cell co-cultures depends on both Toll-like receptor (TLR) 2 and antigen presentation. Synergy between the innate and adaptive responses was also shown when TLR2−/− mice exhibited impaired intraabdominal abscess formation in response to B. fragilis. Commensal bacteria, using molecules like PSA, potentially modulate the Th1/Th2 cell balance and the response to infection by coordinating both the innate and adaptive pathways.
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2
Abbreviations used: BMDC, bone marrow–derived DC; HEK, human embryonic kidney; iNOS, inducible NO synthase; MALP-3, macrophage-activating lipopeptide 3; MHCII, MHC class II; PAMP, pathogen-associated molecular pattern; PSA, polysaccharide A; SCC, sterilized cecal contents; SEA, staphylococcal enterotoxin A; Sp1, type 1 Streptococcus pneumoniae capsular polysaccharide; TLR, Toll-like receptor; ZPS, zwitterionic polysaccharide.
Qun Wang, Rachel M. McLoughlin, Brian A. Cobb, Marie Charrel-Dennis, Kathleen J. Zaleski, Douglas Golenbock, Arthur O. Tzianabos, Dennis L. Kasper; A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2 . J Exp Med 25 December 2006; 203 (13): 2853–2863. doi: https://doi.org/10.1084/jem.20062008
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