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

被引：81

作者：

Laarman, Alexander J. ^{[1
]}

Mijnheer, Gerdien ^{[1
]}

Mootz, Joe M. ^{[2
]}

van Rooijen, Willemien J. M. ^{[1
]}

Ruyken, Maartje ^{[1
]}

Malone, Cheryl L. ^{[2
]}

Heezius, Erik C. ^{[1
]}

Ward, Richard ^{[3
]}

Milligan, Graeme ^{[3
]}

van Strijp, Jos A. G. ^{[1
]}

de Haas, Carla J. C. ^{[1
]}

Horswill, Alexander R. ^{[2
]}

van Kessel, Kok P. M. ^{[1
]}

Rooijakkers, Suzan H. M. ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands

[2] Univ Iowa, Dept Microbiol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA

[3] Univ Glasgow, Inst Mol Cell & Syst Biol, Coll Med Vet & Life Sci, Mol Pharmacol Grp, Glasgow G12 8QQ, Lanark, Scotland

来源：

EMBO JOURNAL | 2012年 / 31卷 / 17期

关键词：

CXCR2; immune evasion; proteases; Staphylococcus aureus; CHEMOKINE RECEPTOR CXCR2; CYSTEINE PROTEASES; MURINE MODEL; EXPRESSION; PROTEIN; IL-8; DEGRADATION; SPECIFICITY; RECRUITMENT; VIRULENCE;

D O I：

10.1038/emboj.2012.212

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 under-stood. 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. The EMBO Journal (2012) 31, 3607-3619. doi: 10.1038/emboj.2012.212; Published online 31 July 2012 Subject Categories: immunology; microbiology & pathogens

引用

页码：3607 / 3619

页数：13

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