{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:03:16Z","timestamp":1791453796195,"version":"4.3.3"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pseudomonas aeruginosa is an opportunistic bacterium that can cause serious infection in immunocompromised individuals. Although autophagy may augment immune responses against P. aeruginosa infection in macrophages, the critical components and their role of autophagy in host defense are largely unknown. In this study, we show that P. aeruginosa infection\u2013induced autophagy activates JAK2\/STAT1\u03b1 and increases NO production. Knocking down Atg7 resulted in increased IFN-\u03b3 release, excessive reactive oxygen species, and increased Src homology-2 domain-containing phosphatase 2 activity, which led to lowered phosphorylation of JAK2\/STAT1\u03b1 and subdued expression of NO synthase 2 (NOS2). In addition, we demonstrated the physiological relevance of dysregulated NO under Atg7 deficiency as atg7\u2212\/\u2212 mice were more susceptible to P. aeruginosa infection with increased mortality and severe lung injury than wild-type mice. Furthermore, P. aeruginosa\u2013infected atg7\u2212\/\u2212 mice exhibited increased oxidation but decreased bacterial clearance in the lung and other organs compared with wild-type mice. Mechanistically, atg7 deficiency suppressed NOS2 activity by downmodulating JAK2\/STAT1\u03b1, leading to decreased NO both in vitro and in vivo. Taken together, these findings revealed that the JAK2\/STAT1\u03b1\/NOS2 dysfunction leads to dysregulated immune responses and worsened disease phenotypes.<\/jats:p>","DOI":"10.4049\/jimmunol.1401958","type":"journal-article","created":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T04:14:08Z","timestamp":1419308048000},"page":"1112-1121","source":"Crossref","is-referenced-by-count":38,"title":["Atg7 Enhances Host Defense against Infection via Downregulation of Superoxide but Upregulation of Nitric Oxide"],"prefix":"10.1093","volume":"194","author":[{"given":"Xuefeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota , Grand Forks, ND 58203"},{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota , Grand Forks, ND 58203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xikun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota , Grand Forks, ND 58203"},{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canhua","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota , Grand Forks, ND 58203"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,1]]},"reference":[{"key":"2025030704592794300_r1","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1086\/320737","article-title":"Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections","volume":"183","author":"Roy-Burman","year":"2001","journal-title":"J. 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