Long-term effects of influenza A virus infection on the phenotype of allergic asthma in a mouse model

Infections with influenza A virus (IAV) have strong impact on the local microenvironment, thereby also affecting inflammatory mechanisms in chronic respiratory diseases such as allergic asthma. Up to now, these interactions are however poorly understood.

We are addressing how a preceding IAV infection affects the phenotype of allergic asthma. We use mouse (C57Bl/6) models of IAV infection and allergic asthma. Mice are first intranasally infected with IAV PR8 (H1N1) and 14 days later sensitized intraperitoneally against the model antigen ovalbumin (OVA). Following sensitization, mice are challenged intranasally with OVA to induce allergic airway inflammation. Histological changes, immune cell recruitment, cytokine responses and OVA-specific IgE levels are analyzed and compared between controls, IAV-infected mice and mice with allergic airway inflammation with and without previous IAV infection.

OVA-sensitized and challenged mice exhibited allergic airway inflammation characterized by cell-recruitment to the airways and lungs, eosinophilic inflammation and the production of inflammatory as well as Th2-cytokines. Eosinophilic inflammation was clearly evident in histology. Significant levels of OVA-specific IgE antibodies as well bronchial hyperreactivity were detectable. Sublethal IAV infection is characterized by a transient loss in body weight and mice have typically cleared the virus and recovered by day 14 post infection. Strikingly, mice analyzed more than five weeks after infection (day 39) histologically still showed ongoing inflammation. Analysis of mice that were sensitized and challenged with OVA from day 14 post IAV infection showed significant changes in the phenotype of the allergic airway inflammation and histology, suggesting a long-lasting potential of IAV infections to alter local allergic inflammatory processes.

The interactions between viral pathogens and mechanisms of allergic asthma are manifold and in many aspects are still not understood. We show that apart from exacerbation during acute infection, IAV infection has long lasting impact on the respiratory immune system affecting chronic respiratory diseases such as allergic asthma.