IL-5 produced by natural helper cells suppresses neutrophil function during influenza infection. (P4239)

Abstract

Abstract Interleukin (IL)-5 is a prototypical type II cytokine that is essential for eosinophil maturation and egress out of the bone marrow. We observed that eosinophil numbers progressively increase in the lungs during the course of experimental influenza A virus (IAV) infection in mice as a result of high level production of IL-5 by natural helper cells recruited to the infected lungs. Mice genetically deficient in IL-5 (IL-5 KO) demonstrate increased lung neutrophil numbers and decreased viral titers during the acute phase of IAV infection. However, this phenotype is not recapitulated in mice deficient in eosinophils (PHIL mice) suggesting an eosinophil independent function of IL-5 during infection. Unexpectedly, we found that like eosinophils, >98% of neutrophils express the IL-5 receptor alpha subunit (CD125) in the lung throughout infection. Unlike eosinophils, where ligation of the IL-5R by IL-5 induces phosphorylation of STAT1 and STAT5, engagement of the IL-5R on activated neutrophils results in suppressed pSTAT5 and pSTAT1 signalling as well as decreased expression of the activation marker CD11b. Furthermore, neutrophils treated with IL-5 undergo accelerated cell death in vitro suggesting a potential mechanism for the enhanced neutrophil numbers seen in the IAV infected IL-5 KO. Overall these data suggest that IL-5 may serve a regulatory role during the acute phase of IAV infection by controlling the number (viability) and activation state of recruited neutrophils.