Innate immune responses in fungal asthma enhance antiviral immunity during influenza virus infections

Abstract

Abstract Fungal allergic asthma is a subtype of asthma with high incidence. Although asthmatics are considered an ‘at risk’ group for severe influenza, these patients suffered less severe morbidity and mortality compared to non-asthmatics during the 2009 influenza pandemic. We developed a mouse model of fungal asthma and influenza comorbidities to recapitulate these epidemiologic findings and provide a means to explore mechanisms by which this protection may occur. We hypothesized that eosinophils guide antiviral responses against influenza virus infections in the allergic host. We characterized the immunophenotype of eosinophils in various niches including bone marrow, lymphoid organs, and lungs, in asthma and influenza comorbid conditions in comparison with individual disease conditions. Eosinophils from comorbid mice had high expression of MHCI, PIR-A/B, and CD62L in the lungs and spleens compared to influenza alone. The adoptive transfer of eosinophils led to a reduction in viral burden and increase in airway CD8+ T cells in virus-infected recipients. In addition, eosinophils were able to promote CD8+ T cell activation in vitro and ex vivo, and antigen-loaded eosinophils interacted with CD8+ T cells in vitro. Comorbid mice had more plasma cells in lymphoid organs although mature B cell numbers were similar to influenza alone. Antibody production in these cells was more prominent at early time points in comorbidity but was similar between the groups at late time points. Since eosinophils have been previously shown to regulate B cells and IgA production in the gut, we are now exploring the hypothesis that eosinophil-mediated B cell responses contribute to the increase in neutralizing antibodies noted in mice with asthma and influenza.