Uncoupling of IL-6 signaling and LC3-associated phagocytosis (LAP) drives immunoparalysis during sepsis

Immune deactivation of phagocytes is a central event in pathogenesis of sepsis that remains molecularly unexplored. In particular, how cytokine deregulation induced by sepsis compromises the microbicidal activity of phagocytes and results in secondary infections by opportunistic bacterial and fungal pathogens is incompletely understood. Herein, we identify a master regulatory role of cytokine signaling on LC3-associated phagocytosis (LAP), and reveal that uncoupling of these two processes during sepsis induces immunoparalysis in monocytes/macrophages. Overall design: Patients admitted to the ICU from April 2014 to December 2017 with clinical diagnosis of septic shock and APACHE II score >=8. Patients are sub-catergorized into three groups depending on the intact of LAP activities. RNA were isolated from blood samples for RNAseq profile.