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

• Published in: The FASEB journal 2018-01, Vol.32 (1), p.26-36
• Main Authors: Weiss, Elisabeth, Hanzelmann, Dennis, Fehlhaber, Beate, Klos, Andreas, Loewenich, Friederike D., Liese, Jan, Peschel, Andreas, Kretschme, Dorothee
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Calcium Signaling - immunology; Cell activation; Cell Degranulation - immunology; Cell Line; Cell Movement - immunology; Chemotaxis; Disease Models, Animal; Female; Genes, Bacterial; Homeobox; Homeodomain Proteins - immunology; Homology; Hoxb8; Humans; Infections; innate immunity; Leukocytes; Leukocytes (neutrophilic); Leukocytes - immunology; Ligands; mFpr2; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; neutrophil; Neutrophils - immunology; Peptides; Peritoneum; Phenols; PSMs; Receptors; Receptors, Formyl Peptide - deficiency; Receptors, Formyl Peptide - genetics; Receptors, Formyl Peptide - immunology; Receptors, Lipoxin - immunology; Shape recognition; Staphylococcal Infections - immunology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - immunology; Staphylococcus infections
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201700441r

Leukocytes express formyl‐peptide receptors (FPRs), which sense microbe‐associated molecular pattern (MAMP) molecules, leading to leukocyte chemotaxis and activation. We recently demonstrated that phenol‐soluble modulin (PSM) peptides from highly pathogenic Staphylococcus aureus are efficient ligands for the human FPR2. How PSM detection 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 hy‐pothesis that the mFpr2 is the functional homolog of the human FPR2 and that a mouse infection model represents a suitable model for analyzing the role of PSMs during infection. PSM recognition by mFpr2 shapes leukocyte influx in local infections, the typical infections caused by S. aureus.—Weiss, E., Hanzelmann, D., Fehlhaber, B., Klos, A., von Loewenich, F. D., Liese, J., Peschel, A., Kretschmer, D. Formyl‐peptide receptor 2 governs leukocyte influx in local Staphylococcus aureus infections. FASEB J. 32, 26‐36 (2018). www.fasebj.org