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The Journal of Immunology, 2002, 169: 10-14.
Copyright © 2002 by The American Association of Immunologists


Cutting Edge

Cutting Edge: Role of Toll-Like Receptor 1 in Mediating Immune Response to Microbial Lipoproteins1

Osamu Takeuchi2,*,{dagger}, Shintaro Sato*,{dagger}, Takao Horiuchi*,{dagger}, Katsuaki Hoshino*,{dagger}, Kiyoshi Takeda*,{dagger}, Zhongyun Dong{ddagger}, Robert L. Modlin§ and Shizuo Akira3,*,{dagger}

* Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; {dagger} Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, Osaka, Japan; {ddagger} Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and § Division of Dermatology, Department of Microbiology and Immunology and Molecular Biology Institute, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095

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-{kappa}B 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.




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