Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis in <i>Pseudomonas</i> Sepsis

Abstract

Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure, with high morbidity and mortality. The literature implies that autophagy is a crucial regulator of inflammation in sepsis. In this article, we report that autophagy-related protein 7 (Atg7) is involved in inflammasome activation in <i>Pseudomonas aeruginosa</i> abdominal infection. Following i.p. challenge with <i>P. aeruginosa</i>, <i>atg7^fl/fl</i> mice showed impaired pathogen clearance, decreased survival, and widespread dissemination of bacteria into the blood and lung tissue compared with wild-type mice. The septic <i>atg7^fl/fl</i> mice also exhibited elevated neutrophil infiltration and severe lung injury. Loss of Atg7 resulted in increased production of IL-1β and pyroptosis, consistent with enhanced inflammasome activation. Furthermore, we demonstrated that <i>P. aeruginosa</i> flagellin is a chief trigger of inflammasome activation in the sepsis model. Collectively, our results provide insight into innate immunity and inflammasome activation in sepsis.