Formyl-peptide receptor 2 governs leukocyte influx in local Staphylococcus aureus infections

Leukocytes express formyl-peptide receptors (FPRs), which sensemicrobe-associated molecular pattern (MAMP) molecules, leading to leukocyte chemotaxis and activation. Werecently demonstrated that phenol-soluble modulin (PSM) peptides from highly pathogenic Staphylococcus aureus are efficient ligands for the human FPR2. HowPSMdetection by FPR2 impacts on the course of S. aureus infections has remained unknown. We characterized the specificity of mouse FPR2 (mFpr2) using a receptor-transfected cell line, homeobox b8 (Hoxb8), and primary neutrophils isolated from wild-type (WT) or mFpr2(-/-) mice. The influx of leukocytes into the peritoneum of WT and mFpr2(-/-) mice was analyzed. We demonstrate that mFpr2 is specifically activated by PSMs in mice, and they represent the first secreted pathogen-derived ligands for the mFpr2. Intraperitoneal infection with S. aureus led to lower numbers of immigrated leukocytes in mFpr2(-/-) compared with WT mice at 3 h after infection, and this difference was not observed when mice were infected with an S. aureus PSM mutant. Our data support the hypothesis that themFpr2 is the functional homolog of the human FPR2 and that amouse infectionmodel represents a suitablemodel for analyzing the role ofPSMs during infection. PSMrecognition bymFpr2 shapes leukocyte influx in local infections, the typical infections caused by S. aureus.