Eosinophils are important mediators of lung defense during complex infections 3609

Abstract Description Our previous work identified that allergic airway inflammation protects the host from pathologies associated with influenza virus infection. We identified novel antiviral functions for eosinophils in this model including their ability to promote CD8+ T cell responses. As underlying allergic asthma also protected hosts from severe morbidity and mortality associated with influenza virus and pneumococci, herein we tested the hypothesis that eosinophils were necessary for antibacterial host defense in the lungs. Wild-type, eosinophil/granule protein deficient mice were subjected to our established 3-hit model of Aspergillus fumigatus allergy, influenza, and Streptococcal pneumonia. Eosinophils were important to host defense during co-infection wherein eosinophil-deficient mice in the 3-hit model lost weight and died. Eosinophil defenses included phagocytosis, direct killing of bacteria, and the secretion of antibacterial granule proteins. Additionally, eosinophils utilized multiple receptors for bacterial uptake including the platelet activating factor receptor and TLRs-2,-4, and -6. While eosinophils did not undergo eetosis in response to pneumococci, these cells dynamically became activated in the presence of bacteria marked by upregulation of surface markers MHCII, CD80 and enhanced CD4+ T cell responses. Antibacterial defenses in human eosinophils were even more robust. Thus, in allergic airways, eosinophils play a fundamental role in mucosal immunity. Funding Sources Supported by the American Lung Association; NIH/NIAID R01-AI125481; Plough Foundation Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)