{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:40:56Z","timestamp":1792176056957,"version":"4.4.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013262","name":"State Key Laboratory of Respiratory Disease","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFC2302500"],"award-info":[{"award-number":["2021YFC2302500"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971900"],"award-info":[{"award-number":["81971900"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271871"],"award-info":[{"award-number":["82271871"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["202201011717"],"award-info":[{"award-number":["202201011717"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.jbc.2023.105518","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T17:15:54Z","timestamp":1701364554000},"page":"105518","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":28,"title":["Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2\/HK1-mediated metabolic rewiring"],"prefix":"10.1016","volume":"300","author":[{"given":"Xiaofei","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6628-8934","authenticated-orcid":false,"given":"Yuejun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2618-5571","authenticated-orcid":false,"given":"Shufeng","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2023.105518_bib1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cell.2017.12.031","article-title":"BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis","volume":"172","author":"Kaufmann","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2023.105518_bib2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained immunity: a memory for innate host defense","volume":"9","author":"Netea","year":"2011","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.jbc.2023.105518_bib3","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.chom.2020.05.014","article-title":"BCG vaccination in humans elicits trained immunity via the hematopoietic progenitor compartment","volume":"28","author":"Cirovic","year":"2020","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.jbc.2023.105518_bib4","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.674334","article-title":"Human newborn monocytes demonstrate distinct BCG-induced primary and trained innate cytokine production and metabolic activation in\u00a0vitro","volume":"12","author":"Angelidou","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib5","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.837524","article-title":"Trained immunity: an overview and the impact on COVID-19","volume":"13","author":"Brueggeman","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib6","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/S1473-3099(21)00403-5","article-title":"100 years of Mycobacterium bovis bacille Calmette-Gu\u00e9rin","volume":"22","author":"Lange","year":"2022","journal-title":"Lancet Infect Dis."},{"key":"10.1016\/j.jbc.2023.105518_bib7","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1016\/j.celrep.2016.11.011","article-title":"Immunometabolic pathways in BCG-induced trained immunity","volume":"17","author":"Arts","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2023.105518_bib8","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S1473-3099(20)30714-3","article-title":"BCG: new life for a centenarian vaccine","volume":"21","author":"Aaby","year":"2021","journal-title":"Lancet Infect Dis."},{"key":"10.1016\/j.jbc.2023.105518_bib9","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41585-021-00481-1","article-title":"100 years of Bacillus Calmette-Gu\u00e9rin immunotherapy: from cattle to COVID-19","volume":"18","author":"Lobo","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"10.1016\/j.jbc.2023.105518_bib10","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2020.04.042","article-title":"Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection","volume":"181","author":"Netea","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2023.105518_bib11","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1080\/14760584.2021.1938550","article-title":"COVID-19 pandemic: SARS-CoV-2 specific vaccines and challenges, protection via BCG trained immunity, and clinical trials","volume":"20","author":"Gong","year":"2021","journal-title":"Expert Rev. Vaccines"},{"key":"10.1016\/j.jbc.2023.105518_bib12","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41418-020-00720-9","article-title":"COVID-19 vaccines: where we stand and challenges ahead","volume":"28","author":"Forni","year":"2021","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.jbc.2023.105518_bib13","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2020.08.051","article-title":"Activate: randomized clinical trial of BCG vaccination against infection in the elderly","volume":"183","author":"Giamarellos-Bourboulis","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2023.105518_bib14","doi-asserted-by":"crossref","first-page":"e121","DOI":"10.1002\/mco2.121","article-title":"Trained immunity: a Yin-Yang balance","volume":"3","author":"Hu","year":"2022","journal-title":"MedComm (2020)"},{"key":"10.1016\/j.jbc.2023.105518_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1147476","article-title":"Trained immunity: a \u201cnew\u201d weapon in the fight against infectious diseases","volume":"14","author":"Dagenais","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib16","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.it.2021.12.006","article-title":"BCG vaccination induces cross-protective immunity against pathogenic microorganisms","volume":"43","author":"Soto","year":"2022","journal-title":"Trends Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib17","doi-asserted-by":"crossref","first-page":"10287","DOI":"10.1074\/jbc.RA118.001696","article-title":"Mycobacterium tuberculosis PPE60 antigen drives Th1\/Th17 responses via Toll-like receptor 2-dependent maturation of dendritic cells","volume":"293","author":"Su","year":"2018","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2023.105518_bib18","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.celrep.2015.05.046","article-title":"mTORC1-Induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation","volume":"12","author":"Moon","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2023.105518_bib19","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00269-20","article-title":"Identification of autophagy-inhibiting factors of Mycobacterium tuberculosis by high-throughput loss-of-function screening","volume":"88","author":"Strong","year":"2020","journal-title":"Infect. Immun."},{"key":"10.1016\/j.jbc.2023.105518_bib20","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.cell.2020.09.062","article-title":"M.\u00a0tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity","volume":"183","author":"Khan","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2023.105518_bib21","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.3389\/fimmu.2019.02806","article-title":"BCG-induced cross-protection and development of trained immunity: implication for vaccine design","volume":"10","author":"Covi\u00e1n","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib22","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.3390\/vaccines10071006","article-title":"Fiction and facts about BCG imparting trained immunity against COVID-19","volume":"10","author":"Kaur","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"10.1016\/j.jbc.2023.105518_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.110028","article-title":"Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes","volume":"37","author":"Kong","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2023.105518_bib24","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41577-020-0337-y","article-title":"BCG-induced trained immunity: can it offer protection against COVID-19?","volume":"20","author":"O\u2019Neill","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib25","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/j.cell.2018.09.042","article-title":"Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity","volume":"175","author":"Yao","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2023.105518_bib26","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/s41590-022-01354-4","article-title":"Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut-lung axis","volume":"23","author":"Jeyanathan","year":"2022","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib27","doi-asserted-by":"crossref","first-page":"17537","DOI":"10.1073\/pnas.1202870109","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes","volume":"109","author":"Kleinnijenhuis","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2023.105518_bib28","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/s41568-018-0074-8","article-title":"mTOR signalling and cellular metabolism are mutual determinants in cancer","volume":"18","author":"Mossmann","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.jbc.2023.105518_bib29","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.144260","article-title":"miR-9-5p regulates immunometabolic and epigenetic pathways in \u03b2-glucan-trained immunity via IDH3\u03b1","volume":"6","author":"Su","year":"2021","journal-title":"JCI Insight"},{"key":"10.1016\/j.jbc.2023.105518_bib30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41419-020-03284-1","article-title":"Hepatitis B virus particles activate B cells through the TLR2-MyD88-mTOR axis","volume":"12","author":"Li","year":"2021","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.jbc.2023.105518_bib31","doi-asserted-by":"crossref","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1\u03b1-mediated aerobic glycolysis as metabolic basis for trained immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.jbc.2023.105518_bib38","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.3389\/fimmu.2020.02059","article-title":"Mitigating coronavirus induced dysfunctional immunity for at-risk populations in COVID-19: trained immunity, BCG and \u201cnew old friends.\u201d","volume":"11","author":"Kleen","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib33","article-title":"Research advances for virus-vectored tuberculosis vaccines and latest findings on tuberculosis vaccine development","volume":"13","author":"Hu","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chom.2017.12.010","article-title":"BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity","volume":"23","author":"Arts","year":"2018","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.jbc.2023.105518_bib35","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2020.04.042","article-title":"Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection","volume":"181","author":"Netea","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2023.105518_bib36","doi-asserted-by":"crossref","first-page":"27741","DOI":"10.1073\/pnas.2008410117","article-title":"BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)","volume":"117","author":"Escobar","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2023.105518_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008969","article-title":"\u201cTrained immunity\u201d from Mycobacterium spp. exposure or BCG vaccination and COVID-19 outcomes","volume":"16","author":"Singh","year":"2020","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.jbc.2023.105518_bib32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.jbc.2023.105518_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2021.102206","article-title":"Glutathione synthesis primes monocytes metabolic and epigenetic pathway for \u03b2-glucan-trained immunity","volume":"48","author":"Su","year":"2021","journal-title":"Redox Biol."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925823025462?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925823025462?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T08:58:08Z","timestamp":1773133088000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925823025462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["S0021925823025462"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2023.105518","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2\/HK1-mediated metabolic rewiring","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2023.105518","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"105518"}}