{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:26:40Z","timestamp":1787030800078,"version":"build-2736575974"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RF-2019-12371111"],"award-info":[{"award-number":["RF-2019-12371111"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health-Istituto Superiore di Sanit\u00e0 AIDS Program ISS-2009","award":["RF-ISS-2009-1304225"],"award-info":[{"award-number":["RF-ISS-2009-1304225"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis is one of the deadliest infectious diseases worldwide. Mycobacterium tuberculosis has developed strategies not only to evade host immunity but also to manipulate it for its survival. We investigated whether Mycobacterium tuberculosis exploited the immunogenicity of Ag85B, one of its major secretory proteins, to redirect host antituberculosis immunity to its advantage. We found that administration of Ag85B protein to mice vaccinated with Bacillus Calmette-Gue\u0301rin impaired the protection elicited by vaccination, causing a more severe infection when mice were challenged with Mycobacterium tuberculosis. Ag85B administration reduced Bacillus Calmette-Gu\u00e9rin-induced CD4 T-cell activation and IFN-\u03b3, CCL-4, and IL-22 production in response to Mycobacterium tuberculosis\u2013infected cells. On the other hand, it promoted robust Ag85B-responsive IFN-\u03b3\u2013producing CD4 T cells, expansion of a subset of IFN-\u03b3\/IL-10\u2013producing CD4+FOXP3+Treg cells, differential activation of IL-17\/IL-22 responses, and activation of regulatory and exhaustion pathways, including programmed death ligand 1 expression on macrophages. All this resulted in impaired intracellular Mycobacterium tuberculosis growth control by systemic immunity, both before and after the Mycobacterium tuberculosis challenge. Interestingly, Mycobacterium tuberculosis infection itself generated Ag85B-reactive inflammatory immune cells incapable of clearing Mycobacterium tuberculosis in both unvaccinated and Bacillus Calmette-Gue\u0301rin\u2013vaccinated mice. Our data suggest that Mycobacterium tuberculosis can exploit the strong immunogenicity of Ag85B to promote its own survival and spread. Since Ag85B is normally secreted by replicating bacteria and is commonly found in the lungs of the Mycobacterium tuberculosis\u2013infected host, our findings may advance the understanding on the mechanisms of Mycobacterium tuberculosis pathogenesis and immune evasion.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae014","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T22:59:27Z","timestamp":1705705167000},"page":"1053-1069","source":"Crossref","is-referenced-by-count":6,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    antigen 85B modifies BCG-induced antituberculosis immunity and favors pathogen survival"],"prefix":"10.1093","volume":"115","author":[{"given":"Giovanni","family":"Piccaro","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0 , Viale Regina Elena 299, 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Aquino","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS , Via Mariano Semmola 53, 80131 Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Gigantino","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS , Via Mariano Semmola 53, 80131 Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tirelli","sequence":"additional","affiliation":[{"name":"Core Facilities-Flow Cytometry Area, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299 , 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Core Facilities-Flow Cytometry Area, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299 , 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egidio","family":"Iorio","sequence":"additional","affiliation":[{"name":"Core Facilities-High Resolution NMR Unit, Istituto Superiore di Sanit\u00e0 , Viale Regina Elena 299, 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-0616","authenticated-orcid":false,"given":"Giuseppe","family":"Matarese","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie mediche, Universit\u00e0 di Napoli \u201cFederico II,\u201d \u00a0 Via Sergio Pansini 5, 80131 Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cassone","sequence":"additional","affiliation":[{"name":"Polo d'innovazione della Genomica, Genetica e Biologia , Via Fiorentina 1, 53100 Siena , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2583-5306","authenticated-orcid":false,"given":"Carla","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0 , Viale Regina Elena 299, 00161 Rome , 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