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

Area of Science:

• Immunology
• Microbiology
• Molecular Biology

Background:

• Leukocytes utilize formyl-peptide receptors (FPRs) to detect microbe-associated molecular patterns (MAMPs), initiating chemotaxis and activation.
• Phenol-soluble modulin (PSM) peptides from Staphylococcus aureus are potent ligands for human FPR2.
• The role of PSM detection by FPR2 in S. aureus infections remains largely unexplored.

Purpose of the Study:

• To characterize the specificity of mouse FPR2 (mFpr2) for PSMs.
• To investigate the impact of mFpr2-PSM interaction on leukocyte influx during S. aureus infection in a mouse model.

Main Methods:

• Characterization of mFpr2 specificity using receptor-transfected cell lines (Hoxb8) and primary neutrophils from wild-type (WT) and mFpr2 knockout (mFpr2-/-) mice.
• Analysis of leukocyte influx into the peritoneum of WT and mFpr2-/- mice following intraperitoneal infection with S. aureus.
• Comparison of infection outcomes using WT S. aureus and an S. aureus PSM mutant.

Main Results:

• Mouse FPR2 (mFpr2) is specifically activated by PSMs, representing the first identified secreted pathogen-derived ligands for mFpr2.
• Intraperitoneal S. aureus infection resulted in significantly lower leukocyte infiltration in mFpr2-/- mice compared to WT mice at 3 hours post-infection.
• This difference in leukocyte influx was not observed when using an S. aureus PSM mutant, highlighting the role of PSMs.

Conclusions:

• Mouse FPR2 (mFpr2) functions as the functional homolog of human FPR2.
• The mouse infection model is suitable for studying the role of PSMs in S. aureus infections.
• PSM recognition by mFpr2 critically influences leukocyte recruitment in localized S. aureus infections.