title: Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis inPseudomonasSepsis.
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 inPseudomonas aeruginosaabdominal infection. Following i.p. challenge withP. aeruginosa,atg7fl/flmice showed impaired pathogen clearance, decreased survival, and widespread dissemination of bacteria into the blood and lung tissue compared with wild-type mice. The septicatg7fl/flmice 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 thatP. aeruginosaflagellin is a chief trigger of inflammasome activation in the sepsis model. Collectively, our results provide insight into innate immunity and inflammasome activation in sepsis.
authors.affiliation: 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.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Pu
authors.affiliation: 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.
authors.forename: Changpei
authors.initials: C
authors.lastname: Gan
authors.affiliation: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203.|Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, Jiangsu 221116, People's Republic of China.
authors.forename: Rongpeng
authors.initials: R
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203.
authors.forename: Shirui
authors.initials: S
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong Xinqu, Shanghai Shi 201203, People's Republic of China.
authors.forename: Lefu
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShangXi 710069, People's Republic of China; and min.wu@med.und.edu mafeng@hotmail.co.jp lianghh@nwu.edu.cn.
authors.forename: Haihua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan 610052, People's Republic of China min.wu@med.und.edu mafeng@hotmail.co.jp lianghh@nwu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China; min.wu@med.und.edu mafeng@hotmail.co.jp lianghh@nwu.edu.cn.|Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D000071193:Autophagy-Related Protein 7 / Q000172:deficiency / Q000276:immunology*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology; D015151:Immunoblotting; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology; D000069292:Pyroptosis / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; D058847:Inflammasomes; D000071193:Autophagy-Related Protein 7