The neuroendocrine peptide catestatin activates mast cell-expressed Mrgprb2 to promote bacterial clearance in skin infections 4047

Abstract Description Introduction Mast cells serve as sentinel cells in the skin, influencing pathogen clearance, tissue remodeling, and vascular regulation. Our research has revealed a mast cell-expressed receptor, Mrgprb2, and its human homolog, MRGPRX2, which contribute to bacterial clearance and neurogenic skin inflammation. Recently, a variety of neuroimmune mechanisms have been revealed to mediate bacterial infections, but whether neuropeptide activation of mast cells via Mrgprb2/X2 is one of these mechanisms is unknown. We hypothesize that Mrgprb2/X2 are critical for promoting clearance of bacteria from skin infections through communication with immunomodulatory neuropeptides. Results In wildtype mice, treatment of methicillin-resistant Staphylococcus aureus (MRSA) skin infections with catestatin, a cutaneous neuroendocrine peptide, reduced bacterial load by 35% compared to vehicle control at 24 hours-post-infection. Conversely, in Mrgprb2-deficient mice, catestatin had no effect on bacterial load compared to control. Additionally, catestatin induces the release of multiple proinflammatory mediators via MRGPRX2/b2 by stimulating downstream G protein signalling pathways. Furthermore, catestatin facilitates immune cells’ migration via Mrgprb2. Conclusions Catestatin is an agonist for Mrgprb2/X2, facilitating MRSA clearance from skin infections and a new potential therapeutic target to treat pervasive pathogens. Funding Sources This research was funded by the J.P. Bickell Foundation, NSERC (RGPIN-2022-03453), and CFI. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)