{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:23:36Z","timestamp":1786976616738,"version":"build-2736575974"},"reference-count":80,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018523","name":"Jinan Scientific Research Leader Workshop Project","doi-asserted-by":"publisher","award":["JNL\u20102022050B"],"award-info":[{"award-number":["JNL\u20102022050B"]}],"id":[{"id":"10.13039\/501100018523","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    (MAB) is an increasingly recognized rapidly growing nontuberculous mycobacterial pathogen whose infection is particularly challenging to treat due to its antibiotic resistance and persistence, necessitating the exploration of innovative treatment strategies. In this study, it is demonstrated that punicalagin, a polyphenolic compound derived from pomegranate, enhances macrophage antibacterial activity by promoting autophagy rather than exerting direct bactericidal effects. In THP\u20101 macrophages, punicalagin at 40\u00a0\u00b5\n                    <jats:sc>m<\/jats:sc>\n                    reduced intracellular MAB by 47% at 24\u00a0h post\u2010infection. Mechanistically, punicalagin treatment induced an increase LC3\u2010II\/LC3\u2010I ratio and p62 degradation. It is found that punicalagin promotes autophagy by enhancing mitochondrial stability through upregulating SIRT1 and activating the SIRT1\/FoxO3 axis, which in turn inhibits the PI3K\/Akt\/mTOR pathway. In vivo mouse studies show that punicalagin treatment significantly reduce the MAB burden in the lungs and alleviates the inflammatory cell infiltration in infected lung tissue. The investigation reveals a striking cellular selectivity in its mechanism of action. Punicalagin demonstrates preferential efficacy in interstitial macrophages, while exhibiting little impact on the MAB burden within alveolar macrophages. Transcriptomic analysis of sorted macrophage populations confirms a significant enrichment of autophagy and lysosome\u2010related pathways specifically in IMs from punicalagin\u2010treated mice. Taken together, the findings uncover a novel host\u2010directed therapeutic strategy against MAB infection.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511734","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T12:44:10Z","timestamp":1760445850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Punicalagin Enhances Autophagy Through Sirtuin 1\/FoxO3a Axis to Inhibit Intracellular\n                    <i>Mycobacterium Abscessus<\/i>\n                    Infection"],"prefix":"10.1002","volume":"13","author":[{"given":"Kefan","family":"Bi","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases China\u2010Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hang Zhou Zhe Jiang 310003 China"},{"name":"Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology  Hang Zhou Zhe Jiang 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bihan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases China\u2010Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hang Zhou Zhe Jiang 310003 China"},{"name":"Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology  Hang Zhou Zhe Jiang 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases China\u2010Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hang Zhou Zhe Jiang 310003 China"},{"name":"Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology  Hang Zhou Zhe Jiang 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijin","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases China\u2010Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hang Zhou Zhe Jiang 310003 China"},{"name":"Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology  Hang Zhou Zhe Jiang 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-307X","authenticated-orcid":false,"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases China\u2010Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hang Zhou Zhe Jiang 310003 China"},{"name":"Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology  Hang Zhou Zhe Jiang 310003 China"},{"name":"Jinan Microecological Biomedicine Shandong Laboratory  Jinan Shandong 250022 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