{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:19:14Z","timestamp":1793909954831,"version":"4.8.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union's Horizon 2020 research and innovation program","award":["667837"],"award-info":[{"award-number":["667837"]}]},{"name":"ERC Advanced","award":["833247"],"award-info":[{"award-number":["833247"]}]},{"name":"Spinoza"},{"DOI":"10.13039\/501100003246","name":"Netherlands Organization for Scientific Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Trained immunity amplifies innate immune responses in an antigen-independent manner. This study explored the ability of trained human primary macrophages to modulate the phenotype and function of T cells. Macrophages play an important role in antigen presentation, resulting in T-cell activation and antigen-specific clonal expansion; however, few studies have investigated whether trained immunity induction in macrophages modulates T-cell activation. Here, through surface marker analysis of naive, \u03b2-glucan-, and Bacillus Calmette\u2013Gu\u00e9rin-trained macrophages, we identified 8 distinct macrophage clusters following trained immunity induction. One of these populations showed an increase in surface activation markers CD40 and CD86, as well as major histocompatibility complex molecules. In vitro co-culture of T cells with autologous Bacillus Calmette\u2013Gu\u00e9rin-trained macrophages resulted in a skewing toward TH17 cells. We also observed an increase in TH17 percentage after Bacillus Calmette\u2013Gu\u00e9rin vaccination of human subjects. The bias toward TH17 triggered by trained macrophages required direct T cell to macrophage contact. Trained macrophages potentiated TH17 skewing independently of the antigen presented. While co-cultures of T cells and Bacillus Calmette\u2013Gu\u00e9rin-trained macrophages responded with higher production of interferon-\u03b3 and interleukin-17 after stimulation, no clear shifts toward effector or memory T cells were observed. In conclusion, this study provides evidence that Bacillus Calmette\u2013Gu\u00e9rin-trained macrophages can modulate T-cell function toward a TH17 phenotype, suggesting that Bacillus Calmette\u2013Gu\u00e9rin-induced trained immunity has the potential to enhance not only innate immune responses but also to modify adaptive T-cell immunity.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf123","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:46:34Z","timestamp":1756381594000},"source":"Crossref","is-referenced-by-count":8,"title":["Bacillus Calmette\u2013Gu\u00e9rin-induced trained immunity potentiates TH17 responses in vitro"],"prefix":"10.1093","volume":"117","author":[{"given":"Leonie S","family":"Helder","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GL ,","place":["The Netherlands"]},{"name":"Department of Anesthesiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Geert Grootplein Zuid 10, Nijmegen 6525 GA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-960X","authenticated-orcid":false,"given":"Laszlo A","family":"Groh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GL ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Matzaraki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GL ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"ter Horst","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , Lazarettgasse 14, 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert Jan","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Geert Grootplein Zuid 10, Nijmegen 6525 GA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A B","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GL ,","place":["The Netherlands"]},{"name":"Department of Medical Genetics, Iuliu Ha\u021bieganu University of Medicine and Pharmacy , Pasteur Street 6, Cluj-Napoca 400535 ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GL ,","place":["The Netherlands"]},{"name":"Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn , Carl-Troll Street 31, 53115 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6274-0448","authenticated-orcid":false,"given":"Anaisa V","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GL ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"2025091920401444900_qiaf123-B1","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1111\/imm.12929","article-title":"The roles of resident, central and effector memory CD4 T-cells in protective immunity following infection or vaccination","volume":"154","author":"Gray","year":"2018","journal-title":"Immunology"},{"key":"2025091920401444900_qiaf123-B2","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1086\/315466","article-title":"CD4+ and CD8+ T cells mediate adoptive immunity to aerosol infection of Mycobacterium bovis Bacillus Calmette-Gu\u00e9rin","volume":"181","author":"Feng","year":"2000","journal-title":"J Infect Dis"},{"key":"2025091920401444900_qiaf123-B3","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1046\/j.1365-2567.1999.00840.x","article-title":"Characterization of the memory\/activated T 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