title: Atg7 deficiency impairs host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice.
abstract: Klebsiella pneumoniae (Kp) is a Gram-negative bacterium that can cause serious infections in humans. Autophagy-related gene 7 (Atg7) has been implicated in certain bacterial infections; however, the role of Atg7 in macrophage-mediated immunity against Kp infection has not been elucidated. Here we showed that Atg7 expression was significantly increased in murine alveolar macrophages (MH-S) upon Kp infection, indicating that Atg7 participated in host defense. Knocking down Atg7 with small-interfering RNA increased bacterial burdens in MH-S cells. Using cell biology assays and whole animal imaging analysis, we found that compared with wild-type mice atg7 knockout (KO) mice exhibited increased susceptibility to Kp infection, with decreased survival rates, decreased bacterial clearance, and intensified lung injury. Moreover, Kp infection induced excessive proinflammatory cytokines and superoxide in the lung of atg7 KO mice. Similarly, silencing Atg7 in MH-S cells markedly increased expression levels of proinflammatory cytokines. Collectively, these findings reveal that Atg7 offers critical resistance to Kp infection by modulating both systemic and local production of proinflammatory cytokines.
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Kiswendsida Claude
authors.initials: KC
authors.lastname: Ouedraogo
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Changpei
authors.initials: C
authors.lastname: Gan
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Shirui
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Xikun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota min.wu@med.und.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D000071193:Autophagy-Related Protein 7; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018836:Inflammation Mediators / Q000378:metabolism*; D007710:Klebsiella Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000472:pathogenicity; D015227:Lipid Peroxidation; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D015996:Survival Rate
chemical_list: C502661:Atg7 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D008869:Microtubule-Associated Proteins; D000071193:Autophagy-Related Protein 7
keywords: Gram-negative bacterial infection; alveolar macrophage; autophagy; autophagy-related gene 7; knockout mice; lung injury; reactive oxygen species