Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins.
The Toll-like receptor (TLR) family acts as pattern recognition receptors for pathogen-specific molecular patterns (PAMPs). TLR2 is essential for the signaling of a variety of PAMPs, including bacterial lipoprotein/lipopeptides, peptidoglycan, and GPI anchors. TLR6 associates with TLR2 and recognizes diacylated mycoplasmal lipopeptide along with TLR2. We report here that TLR1 associates with TLR2 and recognizes the native mycobacterial 19-kDa lipoprotein along with TLR2. Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide. In contrast, TLR1(-/-) cells responded normally to diacylated lipopeptide. TLR1 interacts with TLR2 and coexpression of TLR1 and TLR2 enhanced the NF-kappaB activation in response to a synthetic lipopeptide. Furthermore, lipoprotein analogs whose acylation was modified were preferentially recognized by TLR1. Taken together, TLR1 interacts with TLR2 to recognize the lipid configuration of the native mycobacterial lipoprotein as well as several triacylated lipopeptides.
Takeuchi
Osamu
O
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Sato
Shintaro
S
Horiuchi
Takao
T
Hoshino
Katsuaki
K
Takeda
Kiyoshi
K
Dong
Zhongyun
Z
Modlin
Robert L
RL
Akira
Shizuo
S
D000215:Acylation; D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008970:Molecular Weight; D009161:Mycobacterium / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D029721:Drosophila Proteins; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D010455:Peptides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors