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ABSTRACT

 

 

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

 

Gisa Gerold, Khalid Abu Ajaj, Michael Bienert, Hans-Jürgen Laws, Arturo Zychlinsky, Juana de Diego

 

Nature Immunology, 2008, 9, 761–768

 

Keywords: toll-Like Receptors (TLR); bacterial lipoproteines (BLP)

 

Abstract: 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 β3, were required for BLP-induced TLR2-mediated activation of human monocytes. Furthermore, monocytes from patients with Glanzmann thrombasthenia, which lack integrin β3, were completely unresponsive to BLP. In addition, integrin β3 formed a complex with TLR2 and this complex dissociated after BLP stimulation. Notably, vitronectin and integrin b3 coordinated responses to other TLR2 agonists such as lipoteichoic acid and zymosan. Our findings show that vitronectin and integrin β3 contribute to the initiation of TLR2 responses.

 

 

 

 

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