Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis in Pseudomonas Sepsis.

Qinqin Pu, Changpei Gan, Rongpeng Li, Yi Li, Shirui Tan, Xuefeng Li, Yuquan Wei, Lefu Lan, Xin Deng, Haihua Liang, Feng Ma, Min Wu

Journal of immunology (Baltimore, Md. : 1950) 2017 Apr 15

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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 Pseudomonas aeruginosa abdominal infection. Following i.p. challenge with P. aeruginosa, atg7fl/fl 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 atg7fl/fl 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 P. aeruginosa 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. Copyright © 2017 by The American Association of Immunologists, Inc.

Citation

Qinqin Pu, Changpei Gan, Rongpeng Li, Yi Li, Shirui Tan, Xuefeng Li, Yuquan Wei, Lefu Lan, Xin Deng, Haihua Liang, Feng Ma, Min Wu. Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis in Pseudomonas Sepsis. Journal of immunology (Baltimore, Md. : 1950). 2017 Apr 15;198(8):3205-3213