{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:40:44Z","timestamp":1792176044984,"version":"4.4.0"},"reference-count":92,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,4,5]]},"abstract":"<jats:p>Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1\u03b1 axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity\u2013inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity\u2013inducing signaling pathway that could be used in the adjuvant development.<\/jats:p>","DOI":"10.1126\/sciadv.adk8093","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T13:59:01Z","timestamp":1712325541000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":45,"title":["Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-2347","authenticated-orcid":true,"given":"Jin-Chuan","family":"Xu","sequence":"first","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Jiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."},{"name":"National Clinical Research Center for Infectious Disease, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2048-8886","authenticated-orcid":true,"given":"Liang-Fei","family":"Niu","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3975-9079","authenticated-orcid":true,"given":"Jian-Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2689-9627","authenticated-orcid":true,"given":"Douglas B.","family":"Lowrie","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."},{"name":"National Clinical Research Center for Infectious Disease, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8490-4389","authenticated-orcid":true,"given":"Zhidong","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-7686","authenticated-orcid":true,"given":"Shui-hua","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."},{"name":"National Clinical Research Center for Infectious Disease, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-3559","authenticated-orcid":true,"given":"Xiao-Yong","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China."},{"name":"National Clinical Research Center for Infectious Disease, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.10.011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250684"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.121"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00532"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.04.020"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14133073"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13037"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.051"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-64371-7_8"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.09.041"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.216"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit790"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz1080"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-021-03571-0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15071937"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.02.061"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2016.05.033"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2021-007462"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.034"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.05.014"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-019-0633-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1660-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.12.022"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.02.057"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.025"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3070563"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2930255"},{"key":"e_1_3_2_30_2","first-page":"38","article-title":"Differential hydrolysis of molecular species of lipoprotein phosphatidylcholine by groups IIA, V and X secretory phospholipases A2","volume":"1736","author":"Pruzanski W.","year":"2005","unstructured":"W. Pruzanski, L. Lambeau, M. Lazdunsky, W. Cho, J. Kopilov, A. Kuksis, Differential hydrolysis of molecular species of lipoprotein phosphatidylcholine by groups IIA, V and X secretory phospholipases A2. Biochim. Biophys. Acta 1736, 38\u201350 (2005).","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.1.155"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12111354"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2014.00004"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1924"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.12.005"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-020-0346-4"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28509-z"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2019.10.021"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/JCMA.0000000000000768"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2017.01.086"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-018-0055-4"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2018.08.19"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00633-5"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.062"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00277-1"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.05.004"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.03.012"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202870109"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218599110"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02121-21"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180118"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112658"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12952"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab465"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303887"},{"key":"e_1_3_2_56_2","first-page":"317","article-title":"Aldosterone induces trained immunity: The role of fatty acid synthesis","volume":"116","author":"van der Heijden C.","year":"2020","unstructured":"C. van der Heijden, S. T. Keating, L. Groh, L. A. B. Joosten, M. G. Netea, N. P. Riksen, Aldosterone induces trained immunity: The role of fatty acid synthesis. Cardiovasc. Res. 116, 317\u2013328 (2020).","journal-title":"Cardiovasc. Res."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110772"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1039\/D2SC04307F"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.02.013"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605881"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.434"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2019.07.010"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01359-06"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqz349"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu13113877"},{"key":"e_1_3_2_66_2","article-title":"Dietary intake and biomarkers of linoleic acid and risk of prostate cancer in men: A systematic review and dose-response meta-analysis of prospective cohort studies","volume":"1","author":"Yousefi M.","year":"2023","unstructured":"M. Yousefi, Dietary intake and biomarkers of linoleic acid and risk of prostate cancer in men: A systematic review and dose-response meta-analysis of prospective cohort studies. Crit. Rev. Food Sci. Nutr. 1-17, 10.1080\/10408398.2023.2200840 (2023).","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.013"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu15143129"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acuro.2022.06.001"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.4111\/icu.20210340"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.02.050"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.05.023"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.109208"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101320-125133"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14396-9"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1159\/000355628"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c04063"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113985"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2022.2150449"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15443"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-018-1421-z"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-413"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2377"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac202450g"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5b00354"},{"key":"e_1_3_2_86_2","unstructured":"B. C. Hitz The ENCODE uniform analysis pipelines. bioRxiv [Preprint] (2023)."},{"key":"e_1_3_2_87_2","unstructured":"R. Stark G. Brown DiffBind: Differential binding analysis of ChIP-Seq peak data (Cancer Research UK 2011)."},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0337"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs017"},{"key":"e_1_3_2_91_2","first-page":"100141","article-title":"ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu T.","year":"2021","unstructured":"T. Wu, E. Hu, S. Xu, M. Chen, P. Guo, Z. Dai, T. Feng, L. Zhou, W. Tang, L. Zhan, X. Fu, S. Liu, X. Bo, G. Yu, ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).","journal-title":"Innovation"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adk8093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T13:59:08Z","timestamp":1712325548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adk8093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,5]]},"references-count":92,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,4,5]]}},"alternative-id":["10.1126\/sciadv.adk8093"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adk8093","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,5]]},"assertion":[{"value":"2023-09-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadk8093"}}