Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products

Toll-like receptors (TLRs) 2 and 4 are signal transducers for lipopolysacch aride, 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 activa ted cells heterologously expressing TLR2 but not those expressing TLR1 or T LR4. These TLR2-expressing cells were also stimulated by living motile B. b urgdorferi, suggesting that TLR2 recognition of lipoproteins is relevant to natural Borrelia infection, Importantly, a TLR2 antibody inhibited bacteri al lipoprotein/lipopeptide-induced tumor necrosis factor release from human peripheral blood mononuclear cells, and TLR2-null Chinese hamster macropha ges 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 aviu m and Staphylococcus aureus, demonstrating that this receptor can function as a signal transducer for a wide spectrum of bacterial products. We conclu de that diverse pathogens activate cells through TLR2 and propose that this molecule is a central pattern recognition receptor in host immune response s to microbial invasion.