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EMBO J. 2012 Aug 29;31(17):3607-19. doi: 10.1038/emboj.2012.212. Epub 2012 Jul 31.

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

Author information

1
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

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.

PMID:
22850671
PMCID:
PMC3433787
DOI:
10.1038/emboj.2012.212
[Indexed for MEDLINE]
Free PMC Article
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