A Toll-like receptor 2-integrin beta3 complex senses bacterial lipopeptides via vitronectin.
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.
Gerold
Gisa
G
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
Abu Ajaj
Khalid
K
Bienert
Michael
M
Laws
Hans-Jürgen
HJ
Zychlinsky
Arturo
A
de Diego
Juana L
JL
D001426:Bacterial Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D039661:Integrin beta3 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013915:Thrombasthenia / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D019096:Vitronectin / Q000276:immunology* / Q000378:metabolism
D001426:Bacterial Proteins; D039661:Integrin beta3; D051195:Toll-Like Receptor 2; D019096:Vitronectin