A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2.
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-gamma 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.
Wang
Qun
Q
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
McLoughlin
Rachel M
RM
Cobb
Brian A
BA
Charrel-Dennis
Marie
M
Zaleski
Kathleen J
KJ
Golenbock
Douglas
D
Tzianabos
Arthur O
AO
Kasper
Dennis L
DL
D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007113:Immunity, Innate / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism
D051940:B7-2 Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011135:Polysaccharides, Bacterial; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse