A Toll-like receptor 2-integrin β3 complex senses bacterial lipopeptides via vitronectin

被引：72

作者：

Gerold, Gisa ^{[1
]}

Abu Ajaj, Khalid ^{[2
]}

Bienert, Michael ^{[2
]}

Laws, Hans-Juergen ^{[3
]}

Zychlinsky, Arturo ^{[1
]}

de Diego, Juana L. ^{[1
]}

机构：

[1] Max Planck Inst Infect Biol, Dept Cellular Microbiol, D-10117 Berlin, Germany

[2] Leibniz Inst Mol Pharmacol, Dept Peptide Chem & Biochem, D-13125 Berlin, Germany

[3] Dusseldorf Univ Hosp, Dept Pediat Oncol Hematol & Immunol, D-40225 Dusseldorf, Germany

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 07期

关键词：

D O I：

10.1038/ni.1618

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Toll-like receptor 2 (TLR2) initiates inflammation in response to bacterial lipopeptide (BLP). However, the molecular mechanisms enabling the detection of BLP by TLR2 are unknown. Here we investigated the interaction of BLP with human serum proteins and identified vitronectin as a BLP-recognition molecule. Vitronectin and its receptor, integrin beta(3), were required for BLP-induced TLR2-mediated activation of human monocytes. Furthermore, monocytes from patients with Glanzmann thrombasthenia, which lack integrin beta(3), were completely unresponsive to BLP. In addition, integrin beta(3) formed a complex with TLR2 and this complex dissociated after BLP stimulation. Notably, vitronectin and integrin beta(3) coordinated responses to other TLR2 agonists such as lipoteichoic acid and zymosan. Our findings show that vitronectin and integrin beta(3) contribute to the initiation of TLR2 responses.

引用

页码：761 / 768

页数：8

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