Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis

Laarman, A.J. et al. (2012) Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis. EMBO Journal, 31(17), pp. 3607-3619. (doi: 10.1038/emboj.2012.212)

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Abstract

The CXC chemokine receptor 2 (CXCR2) on neutrophils, which recognizes chemokines produced at the site of infection, plays an important role in antimicrobial host defenses such as neutrophil activation and chemotaxis. Staphylococcus aureus is a successful human pathogen secreting a number of proteolytic enzymes, but their influence on the host immune system is not well understood. Here, we identify the cysteine protease Staphopain A as a chemokine receptor blocker. Neutrophils treated with Staphopain A are unresponsive to activation by all unique CXCR2 chemokines due to cleavage of the N-terminal domain, which can be neutralized by specific protease inhibitors. Moreover, Staphopain A inhibits neutrophil migration towards CXCR2 chemokines. By comparing a methicillin-resistant S. aureus (MRSA) strain with an isogenic Staphopain A mutant, we demonstrate that Staphopain A is the only secreted protease with activity towards CXCR2. Although the inability to cleave murine CXCR2 limits in-vivo studies, our data indicate that Staphopain A is an important immunomodulatory protein that blocks neutrophil recruitment by specific cleavage of the N-terminal domain of human CXCR2.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ward, Dr Richard and Milligan, Professor Graeme
Authors: Laarman, A.J., Mijnheer, G., Mootz, J.M., van Rooijen, W.J.M., Ruyken, M., Malone, C.L., Heezius, E.C., Ward, R., Milligan, G., van Strijp, J.A.G., de Haas, C.J.C., Horswill, A.R., van Kessel, K.P.M., and Rooijakkers, S.H.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:EMBO Journal
ISSN:0261-4189

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