Article abstract
Nature Immunology 9, 761 - 768 (2008)
Published online: 30 May 2008 | doi:10.1038/ni.1618
A Toll-like receptor 2–integrin 
3 complex senses bacterial lipopeptides via vitronectin
Gisa Gerold1, Khalid Abu Ajaj2, Michael Bienert2, Hans-Jürgen Laws3, Arturo Zychlinsky1 & Juana L de Diego1
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 
3, were required for BLP-induced TLR2-mediated activation of human monocytes. Furthermore, monocytes from patients with Glanzmann thrombasthenia, which lack integrin 3, were completely unresponsive to BLP. In addition, integrin 3 formed a complex with TLR2 and this complex dissociated after BLP stimulation. Notably, vitronectin and integrin 3 coordinated responses to other TLR2 agonists such as lipoteichoic acid and zymosan. Our findings show that vitronectin and integrin 3 contribute to the initiation of TLR2 responses.
- Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
- Department of Peptide Chemistry and Biochemistry, Leibniz Institute for Molecular Pharmacology, 13125 Berlin, Germany.
- Department of Pediatric Oncology, Hematology and Immunology, Düsseldorf University Hospital, 40225 Düsseldorf, Germany.
Correspondence to: Juana L de Diego1 e-mail: diego@mpiib-berlin.mpg.de
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