title: Annexin A2 Regulates Autophagy in Pseudomonas aeruginosa Infection through the Akt1-mTOR-ULK1/2 Signaling Pathway.
abstract: Earlier studies reported that a cell membrane protein, Annexin A2 (AnxA2), plays multiple roles in the development, invasion, and metastasis of cancer. Recent studies demonstrated that AnxA2 also functions in immunity against infection, but the underlying mechanism remains largely elusive. Using a mouse infection model, we reveal a crucial role for AnxA2 in host defense against Pseudomonas aeruginosa, as anxa2(-/-) mice manifested severe lung injury, systemic dissemination, and increased mortality compared with wild-type littermates. In addition, anxa2(-/-) mice exhibited elevated inflammatory cytokines (TNF-α, IL-6, IL-1β, and IFN-γ), decreased bacterial clearance by macrophages, and increased superoxide release in the lung. We further identified an unexpected molecular interaction between AnxA2 and Fam13A, which activated Rho GTPase. P. aeruginosa infection induced autophagosome formation by inhibiting Akt1 and mTOR. Our results indicate that AnxA2 regulates autophagy, thereby contributing to host immunity against bacteria through the Akt1-mTOR-ULK1/2 signaling pathway.
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203; College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211800, People's Republic of China;
authors.forename: Rongpeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203; College of Agriculture, Yunnan University, Kunming 650091, People's Republic of China;
authors.forename: Shirui
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203; Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China; and.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203;
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jundt
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203; State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203; min.wu@med.und.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000276:immunology*; D001343:Autophagy / Q000235:genetics / Q000276:immunology; D000071189:Autophagy-Related Protein-1 Homolog; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology*; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D017306:Annexin A2; D016207:Cytokines; C546843:mTOR protein, mouse; C401061:Ulk2 protein, mouse; C514862:Akt1 protein, mouse; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C112444:Ulk1 protein, mouse