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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / immunology*
  • Cells, Cultured
  • Chemotaxis, Leukocyte / immunology
  • Cysteine Endopeptidases / immunology*
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Activation / immunology
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology*
  • Receptors, Interleukin-8B / antagonists & inhibitors
  • Receptors, Interleukin-8B / immunology*
  • U937 Cells


  • Bacterial Proteins
  • Receptors, Interleukin-8B
  • Cysteine Endopeptidases
  • staphopain A protein, Staphylococcus aureus