Discrimination of bacterial lipoproteins by Toll-like receptor 6.
Bacterial lipoproteins (BLP) trigger immune responses via Toll-like receptor 2 (TLR2) and their immunostimulatory properties are attributed to the presence of a lipoylated N-terminus. Most BLP are triacylated at the N-terminus cysteine residue, but mycoplasmal macrophage-activating lipopeptide-2 kD (MALP-2) is only diacylated. Here we show that TLR6-deficient (TLR6(-/-)) cells are unresponsive to MALP-2 but retain their normal responses to lipopeptides of other bacterial origins. Reconstitution experiments in TLR2(-/-) TLR6(-/-) embryonic fibroblasts reveal that co-expression of TLR2 and TLR6 is absolutely required for MALP-2 responsiveness. Taken together, these results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria.
Takeuchi
O
O
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Kawai
T
T
Mühlradt
P F
PF
Morr
M
M
Radolf
J D
JD
Zychlinsky
A
A
Takeda
K
K
Akira
S
S
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D029721:Drosophila Proteins; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D055666:Lipopeptides; D008074:Lipoproteins / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D009842:Oligopeptides / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001426:Bacterial Proteins; D029721:Drosophila Proteins; D015850:Interleukin-6; D055666:Lipopeptides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009842:Oligopeptides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495368:TLR6 protein, human; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; C106335:macrophage stimulatory lipopeptide 2