Toll-like Receptor 2 Functions as a Pattern Recognition Receptor for Diverse Bacterial Products

作者：Egil Lien, Timothy J. Sellati, Atsutoshi Yoshimura, Trude Helen Flo, Georges Rawadi, Robert W. Finberg, J. David Carroll, Terje Espevik, Robin R. Ingalls, Justin D. Radolf, Douglas Taylor Golenbock · 发表于：Journal of Biological Chemistry · 年份：1999 · DOI：10.1074/jbc.274.47.33419 · 被引用次数：929 · 研究领域：Immune Response and Inflammation、Antimicrobial Peptides and Activities、Vector-borne infectious diseases

Toll-like receptors (TLRs) 2 and 4 are signal transducers for lipopolysaccharide, the major proinflammatory constituent in the outer membrane of Gram-negative bacteria. We observed that membrane lipoproteins/lipopeptides from Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans activated cells heterologously expressing TLR2 but not those expressing TLR1 or TLR4. These TLR2-expressing cells were also stimulated by living motile B. burgdorferi, suggesting that TLR2 recognition of lipoproteins is relevant to natural Borrelia infection. Importantly, a TLR2 antibody inhibited bacterial lipoprotein/lipopeptide-induced tumor necrosis factor release from human peripheral blood mononuclear cells, and TLR2-null Chinese hamster macrophages were insensitive to lipoprotein/lipopeptide challenge. The data suggest a role for the native protein in cellular activation by these ligands. In addition, TLR2-dependent responses were seen using whole Mycobacterium avium and Staphylococcus aureus, demonstrating that this receptor can function as a signal transducer for a wide spectrum of bacterial products. We conclude that diverse pathogens activate cells through TLR2 and propose that this molecule is a central pattern recognition receptor in host immune responses to microbial invasion.