ID: 8: Innate immune defense against influenza virus infection

Abstract

The mucosal surfaces represent major sites of entry for numerous infectious agents. Consequently, the vast mucosal surfaces are intricately lined with cells and lymphoid organs specialized in providing protective antibody and cellular immunity. Our laboratory’s goal is to understand how immunity is initiated and maintained at the mucosal surfaces that serve as natural portals of entry for pathogens of significant health concerns in the world. In this study, we focused on understanding how viruses are recognized by the innate immune system and how that information is used to generate protective immunity. The myxovirus resistance protein 1 (Mx1) is a dynamin-like GTPase that blocks primary transcription of influenza presumably by binding to viral nucleoproteins. Many inbred laboratory mouse strains have mutations in the Mx1 gene including the C57BL/6 mice. By using mice that have intact Mx1, we demonstrate the critical role of innate sensors in viral control. Further, we reveal a lethal consequence of triggering caspase-1 activation in the absence of innate resistance. Therefore, our results demonstrate that caspase-1 in the absence of antiviral resistance can trigger lethal disease and such conditions may underlie vulnerability to IAV disease in humans.