Mast cell function is impaired via MAPK inhibition by Pseudomonas aeruginosa quorum sensing molecules 4528

Abstract Description Introduction Mast cells are found in tissues adjacent to the external environment like skin, lungs, and intestine, and play a crucial role in host defense. To evade immune responses, bacteria like Pseudomonas aeruginosa, which forms antibiotic-resistant biofilms through quorum sensing, may suppress mast cell function. While P. aeruginosa quorum sensing molecules (QSMs) are known to affect various immune cells, their impact on mast cells remains unclear. We recently identified that mast cells can detect QSMs through surface receptors. We hypothesize that P. aeruginosa QSMs disrupt mast cell immune functions by interfering with receptor-mediated signaling pathways. Aims: 1. Determine if P. aeruginosa QSMs affect FcεRI- and MRGPRX2-mediated mast cell mediator release. 2. To dissect the underlying signaling mechanism impacted by P. aeruginosa QSMs. Results P. aeruginosa QSMs inhibit human mast cell degranulation and histamine release through impairment of FcεRI- and MRGPRX2-induced intracellular calcium mobilization. Moreover, these QSMs attenuate the release of de novosynthesized proinflammatory mediators and prevent PI3K and ERK1/2 phosphorylation in both FceRI- and MRGPRX2-activated human mast cells. Conclusions P. aeruginosa QSMs are inhibitors of FcεRI and MRGPRX2 G protein-coupled receptor pathways of mast cell activation. This work advances our knowledge in crucial areas of host-pathogen interactions and opens new avenues for targeting antimicrobial-resistant pathogens. Funding Sources This research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN-2022-03453), the Canada Foundation for Innovation, and the College of Biological Science Team Building Grant. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)