Asthma is a chronic airway disease characterized by allergic inflammation, airway hyperresponsiveness and tissue remodeling. Influenza infections can lead to severe exacerbations in asthma patients. However, the underlying mechanisms of how antiviral responses to influenza change in asthma remain unclear. In this study, we aimed to investigate how pre-existing allergic inflammation changes responses to influenza infection in mice exposed to house dust mite (HDM).

Mice were exposed to HDM, followed by influenza virus infection, and sacrificed 3 days post infection. HDM-specific immunoglobulins were assessed in plasma and lung tissue was used for flow cytometry analysis and RNA-seq analysis.

HDM exposure resulted in more eosinophils, neutrophils, Th1 cells and Th17 cells, as well as higher production of HDM-specific immunoglobulins IgE, IgG1, and IgG2. Hence, HDM exposure induced important features of allergic lung inflammation. Upon influenza infection, we observed that the effects of HDM and influenza interacted, resulting in fewer Th1 cells, regulatory T cells and more Th2 cells in infected HDM-exposed mice compared to either exposure alone. Interestingly, RNA-seq analysis showed that genes associated with Th1/Treg development (Ms4a4b, Oas1h, and IL7) were also lower expressed in infected HDM-exposed mice compared to either exposure alone. This may suggest impaired Th1/Treg development or migration of these cells in infected allergic lung tissue.

Th1 cells are important in antiviral responses and their specific absence in allergic lung tissue infected with influenza may explain why patients with asthma are more prone to severe viral disease when infected with influenza virus.