A Toll-like receptor 2-integrin beta(3) complex senses bacterial lipopeptides via vitronectin

作者：Gerold Gisa; Abu Ajaj Khalid; Bienert Michael; Laws Hans Juergen; Zychlinsky Arturo; de Diego Juana L^*

来源：Nature Immunology, 2008, 9(7): 761-768.

DOI：10.1038/ni.1618

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.

• 出版日期2008-7