MLKL-Driven Inflammasome Activation and Caspase-8 Mediate Inflammatory Cell Death in Influenza A Virus Infection
Xuqiu Lei, Yongzhi Chen, Egil Lien, Katherine A. Fitzgerald
Abstract
Influenza A virus (IAV) induces multiple types of cell death, which play important roles in the host antiviral responses but can also cause unwanted inflammation and tissue damage. In this study, we dissect the interplay of cell death pathways and demonstrate that macrophages utilize redundant mechanisms to drive an inflammatory form of cell death upon IAV infection. MLKL, the executor of necroptosis, promotes inflammasome activation and pyroptotic cell death. When the MLKL-inflammasome axis is inhibited, cells divert to caspase-8-dependent inflammatory cell death. Our findings advance the current understanding of the innate immune response to IAV infection as well as broader contexts involving multifaceted cell death.