Pseudomonas aeruginosa-infected Myeloid-derived suppressor cells (MDSC) down-regulate lymphocyte activity and improves mice survival, followingin vivolung transfer

Abstract

ABSTRACTPseudomonas aeruginosa(P.a.) is a pathogenic opportunistic bacterium, classified as a priority by the WHO for the research of new treatments. As this bacterium is harmful trough the inflammation and tissue damage it causes, we investigated the role of Myeloid Derived Suppressor Cells (MDSC) inP.a.infections and their potential as a therapeutic target. We found that uponP.a.exposure, MDSC activity is increased and gain contact-independent properties. Interestingly, this activation is dependent onP.a.mobility but not its flagellin nor TLR5-MyD88 pathway. We also show that MDSC adoptive transfer increases mice survival inP.a.acute lung infection both in therapeutic and prophylactic set ups. Finally, usingan in vitroscratch assay model, we suggest that MDSC acts directly on lung epithelium to stimulate its repair. Together, we highlight a potential beneficial role of MDSC inP.a.infection response. We believe that the unique properties of MDSC make them attractive potential new therapeutic tools for patients with acute or chronic inflammatory diseases, where inflammation has to be kept in check.