Analysis of genes associated with pulmonary mucosal defense against influenza A virus infection (INM8P.402)

Abstract

Abstract Influenza A virus infects affect a large population worldwide every year. Antigenic drifts and shifts, and re-assortments in influenza A viruses contribute to reduced host protection. Early host immune defenses may also vary based on the virus strain. A murine model system is one of the best in vivo models to study the host immune defense against Influenza A virus. We hypothesized that host mucosal defenses are initiated in the lung mucosa by expression of antimicrobial peptides. We infected C57BL/6 female mice with 1000 TCID50 A/CA/04/2009 (pH1N1) or A/PR/08/1934 (PR8) strains of influenza A virus and quantified changes in cell recruitment and antimicrobial peptide gene expression at 0, 1, 3, 9, 24, 48, and 120 hours. Both viruses efficiently replicated in mice with peak viral production at 48 hours. However, PR8 caused more damage to the host, marked by increased recruitment of neutrophils, lymphocytes and macrophages and viral burden compared to pH1N1. Genes associated with antimicrobial peptides (RELM, MBD4, CRAMP, PLUNC) were upregulated starting at 3 hours post infection. These genes were more highly expressed in response to PR8 virus. Our data suggest that the proteins encoded by these genes may initiate the immune response against influenza A virus infections and that the host mucosal response varies depending on the strain of virus.