Hannah Bone

Abstract Type III interferons (IFNλ) are innate immune cytokines that limit viral replication and coordinate tissue repair through the induction of interferon stimulated genes (ISGs). This response must be tightly regulated to avoid excessive responses that result in the disruption of tissue barrier integrity or inefficient responses that allow for pathogen escape. Here we examine the contribution of Mitogen Activated Protein Kinase (MAPK) signaling on IFNλ-mediated antiviral activity.

Abstract Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd−/−) significantly attenuates influenza virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads.

1 INTRODUCTION Mitochondrial dysfunction and aberrant cellular metabolism have emerged as critical drivers of many disease processes in humans, including cancer, diabetes, and fibrosis of the lungs and other organs (Alcalá et al., 2017; Loomba et al., 2021; Watanabe et al., 2008). Under homeostatic conditions, cellular energy requirements are largely met by mitochondrial respiration driven by the tricarboxylic acid (TCA) cycle.