Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus

Cell Host Microbe. 2010 Jun 25;7(6):463-73. doi: 10.1016/j.chom.2010.05.012.


Virulence of emerging community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and other highly pathogenic S. aureus strains depends on their production of phenol-soluble modulin (PSM) peptide toxins, which combine the capacities to attract and lyse neutrophils. The molecular basis of PSM-stimulated neutrophil recruitment has remained unclear. Here, we demonstrate that the human formyl peptide receptor 2 (FPR2/ALX), which has previously been implicated in control of endogenous inflammatory processes, senses PSMs at nanomolar concentrations and initiates proinflammatory neutrophil responses to CA-MRSA. Specific blocking of FPR2/ALX or deletion of PSM genes in CA-MRSA severely diminished neutrophil detection of CA-MRSA. Furthermore, a specific inhibitor of FPR2/ALX and of its functional mouse counterpart blocked PSM-mediated leukocyte infiltration in vivo in a mouse model. Thus, the innate immune system uses a distinct FPR2/ALX-dependent mechanism to specifically sense bacterial peptide toxins and detect highly virulent bacterial pathogens. FPR2/ALX represents an attractive target for new anti-infective or anti-inflammatory strategies.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Toxins / metabolism*
  • Community-Acquired Infections / microbiology
  • Female
  • Host-Pathogen Interactions*
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity*
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Protein Binding
  • Receptors, Formyl Peptide / metabolism*
  • Receptors, Formyl Peptide / physiology
  • Receptors, Lipoxin / metabolism*
  • Staphylococcal Infections


  • Bacterial Toxins
  • FPR2 protein, human
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • formyl peptide receptor 2, mouse
  • staphylococcal delta toxin