Pu Qinqin, Gan Changpei, Li Rongpeng, Li Yi, Tan Shirui, Li Xuefeng, Wei Yuquan, Lan Lefu, Deng Xin, Liang Haihua, Ma Feng, Wu Min
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203.
J Immunol. 2017 Apr 15;198(8):3205-3213. doi: 10.4049/jimmunol.1601196. Epub 2017 Mar 3.
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 abdominal infection. Following i.p. challenge with , 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 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 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.
脓毒症是一种严重且复杂的综合征，其特征为宿主炎症反应失调和器官衰竭，发病率和死亡率都很高。文献表明自噬是脓毒症炎症的关键调节因子。在本文中，我们报告自噬相关蛋白7（Atg7）参与腹部感染中的炎性小体激活。经腹腔注射 攻击后，与野生型小鼠相比， 小鼠表现出病原体清除受损、存活率降低以及细菌广泛扩散至血液和肺组织。脓毒症 小鼠还表现出中性粒细胞浸润增加和严重的肺损伤。Atg7缺失导致IL-1β产生增加和细胞焦亡，这与炎性小体激活增强一致。此外，我们证明鞭毛蛋白是脓毒症模型中炎性小体激活的主要触发因素。总的来说，我们的结果为脓毒症中的固有免疫和炎性小体激活提供了见解。
