Eosinophils undergo temporally regulated phenotypic and physiologic changes during influenza A virus infection

Abstract

Abstract Eosinophils are traditionally known for their antiparasitic responses and as biomarkers of allergic diseases, including asthma. Using our model of asthma and influenza (AF) co-morbidity wherein disease outcomes varied by the presence of eosinophils in the airways, we determined that eosinophils played a dynamic antiviral role during influenza A virus (IAV) infections mainly by regulating CD8+ T cell immunity. We have also found that eosinophils in different niches including bone marrow, lymphoid organs, and lungs, undergo distinct immunophenotypic changes depending on the disease state in mice with asthma, influenza, or AF co-morbidity. Therefore, we hypothesized that eosinophil activation and migratory capacity are temporally regulated during IAV infection and that these changes in eosinophils are sensitive to the environment. Virus-exposure resulted in the upregulation of ICAM-1, CD69, and CD11b and downregulation of CD62L on eosinophils within 20 minutes. This expression pattern was temporally regulated suggestive of their ability sense IAV and alter functional responses such as migratory potential. Furthermore, mice infected with eosinophil pre-exposed IAV had a significantly reduced viral burden in the lungs. Eosinophils prevented IAV-induced cytopathology on lung epithelial cells when co-cultured directly or separated by transwell. In addition, eosinophil recipient IAV-infected mice showed no damage to the bronchial airway epithelium. Cumulatively, these data suggest a direct antiviral role for eosinophils through self-activation, reducing virus infectivity, and protecting the respiratory barrier from virus-induced damage further establishing an antiviral role for eosinophils in allergic airways.