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Staphylococcus aureus Staphopain A inhibits CXCR2‐dependent neutrophil activation and chemotaxis
Author(s) -
Laarman Alexander J,
Mijnheer Gerdien,
Mootz Joe M,
van Rooijen Willemien J M,
Ruyken Maartje,
Malone Cheryl L,
Heezius Erik C,
Ward Richard,
Milligan Graeme,
van Strijp Jos A G,
de Haas Carla J C,
Horswill Alexander R,
van Kessel Kok P M,
Rooijakkers Suzan H M
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.212
Subject(s) - chemotaxis , biology , staphylococcus aureus , microbiology and biotechnology , cxc chemokine receptors , neutrophile , immunology , bacteria , chemokine , chemokine receptor , inflammation , receptor , genetics
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.