Discrimination of bacterial lipoproteins by Toll-like receptor 6

Bacterial lipoproteins (BLP) trigger immune responses via Toll-like recepto r 2 (TLR2) and their Immunostimulatory properties are attributed to the pre sence of a lipoylated N-terminus. Most BLP are triacylated at the N-terminu s cysteine residue, but mycoplasmal macrophage-activating lipopeptide-2 kD (MALP-2) is only diacylated. Here we show that TLR6-deficient (TLR6(-/-)) c ells are unresponsive to MALP-2 but retain their normal responses to lipope ptides of other bacterial origins. Reconstitution experiments in TLR2(-/-) TLR6(-/-) embryonic fibroblasts reveal that coexpression of TLR2 and TLR6 i s absolutely required for MALP-2 responsiveness. Taken together, these resu lts show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears t o discriminate between the N-terminal lipoylated structures of MALP-2 and l ipopeptides derived from other bacteria.