The effect of lipopolysaccharide (LPS) on post-viral airway disease is independent of the Type I interferon receptor

Abstract Rationale Sendai virus (SeV, murine parainfluenza virus type 1) infection of C57BL6 (WT) mice leads to post-viral airway disease, characterized by airway hyperreactivity (AHR). Previous data suggested pretreatment of WT mice with lipopolysaccharide (LPS) decreased post-viral airway disease in a dose dependent manner. LPS binding to its receptor can trigger release of type I interferon (IFN), which is a critical anti-viral cytokine. Type I IFN is known to restrict viral replication and spread. However, the role type I IFN mediates in LPS protection from post-viral airway disease is not known. This study was undertaken to determine if the LPS mediated reduction of AHR depended upon type I IFN signaling. Methods WT and Ifnar−/− mice (mice with genetic deletion of the type I IFN receptor) were inoculated intranasally with 30 ul 0.1 μg LPS (dose that inhibited post-viral disease in prior studies) or PBS 24 hours before SeV (2e5 pfu) or UV inactivated SeV. Twenty-one days post-viral inoculation, AHR was determined by invasive measurement of airways’ resistance to methacholine. Results SeV induced a similar level of AHR in both Ifnar−/−and WT mice when they were pretreated with PBS. Similarly, pretreatment of Ifnar−/− mice with LPS significantly reduced AHR compared to PBS treated Ifnar−/− mice (p<0.0001, ANOVA, n≥3). LPS treated Ifnar−/− mice demonstrated significantly reduced AHR compared to PBS treated WT mice, as well (p=0.001, n≥3). Conclusion LPS mediated reduction of post-viral airway disease is independent of type I IFN receptor signaling. Our results suggest LPS prevents post-viral AHR independent of IFNAR signaling. Future studies will determine other mechanisms through which LPS pre-treatment prevents post-viral AHR.