As innate immune cells, neutrophils play a critical role in defending the human body against invading pathogens. To detect foreign organisms and initiate an immune response, neutrophils use a set of pattern-recognition receptors (PRRs) that are activated by pathogen-associated molecular patterns (PAMPs). These PRRs include the formyl-peptide receptors (FPRs). While FPR1 senses short formylated peptides of bacteria in general, FPR2 is activated by specific bacterial molecules including phenol-soluble modulins (PSMs). PSMs are small toxic peptides produced in high amounts by the pathogenic bacterium Staphylococcus aureus. Both FPR1 and FPR2 ligands stimulate neutrophils to release cytokines like IL-8 and produce reactive oxygen species (ROS) or guide neutrophil chemotaxis.

Since both FPR1 ligands and PSMs as FPR2 ligands are present at the site of infection with S. aureus, the aim of this work is to analyse the impact of co-stimulation of FPR1 and FPR2 on neutrophils. Preliminary data indicate that the activation of both receptors synergistically enhances the release of the chemokine IL-8 and the antimicrobial peptide LL-37 by neutrophils. Likewise, cell migration and ROS production are increased, resulting in an overall higher inflammatory immune response.

Activation of FPRs plays an important role during an immune response. Therefore, deciphering the interaction between FPR1 and FPR2 promises to shed light on the regulation of inflammation and pave the way for the development of new therapeutic approaches.