{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:52:58Z","timestamp":1791553978065,"version":"4.3.4"},"reference-count":36,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFD1800403"],"award-info":[{"award-number":["2021YFD1800403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32573357"],"award-info":[{"award-number":["32573357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Priority Academic Development Program of Jiangsu Higher Education Institutions","award":["PADP"],"award-info":[{"award-number":["PADP"]}]},{"name":"111 Project","award":["D18007"],"award-info":[{"award-number":["D18007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterium tuberculosis (M. tb) is a leading cause of infectious disease mortality worldwide, and M. tb subverts host immunity to persist intracellularly. Type I interferon (IFN-I) modulates host defense during M. tb infection, but the mechanisms controlling their induction remain incompletely defined. In this research, a previously uncharacterized mycobacterial factor, M. tb Rv3248c, which regulates IFN-I response, was identified using pull-down and mass spectrometry. Overexpression of Rv3248c suppresses IFN-\u03b2 expression in macrophages at both the transcriptional and protein levels. In addition, it also enhances intracellular bacterial load, whereas in bone marrow-derived macrophages (BMDMs) from Ifnar1\u2013\/\u2013 C57BL\/6 mice, the difference of bacterial load was no longer statistically significant, suggesting that Rv3248c enhances mycobacterial survival in IFN-I-dependent manner. Furthermore, the study shows that M. tb Rv3248c inhibits IFN-I response via the cGAS-STING pathway. Mechanistically, Rv3248c binds TANK-binding kinase 1 (TBK1) and promotes its ubiquitination-mediated proteasomal degradation. The N-terminal region of Rv3248c (amino acids 1\u2013134) is required for TBK1 interaction and IFN-I inhibition. These findings identify a previously uncharacterized mechanism by which M. tb dampens the IFN-I response by targeting TBK1, highlighting Rv3248c as a contributor to pathogenesis and a potential therapeutic target.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00364","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:02:04Z","timestamp":1790078524000},"page":"3385-3397","source":"Crossref","is-referenced-by-count":0,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    Rv3248c Inhibits Type\nI Interferon Response and Promotes Intracellular\nSurvival by Mediating Ubiquitin-Proteasome-Dependent Degradation of\nTBK1"],"prefix":"10.1021","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-2155","authenticated-orcid":true,"given":"Zhengzhong","family":"Xu","sequence":"first","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Geng","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Wu","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Wan","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengkun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]},{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]},{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-an","family":"Jiao","sequence":"additional","affiliation":[{"name":"Yangzhou University , , ,","place":["Yangzhou, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"12","key":"2026100909102391900_cit1","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/cmi.2017.88","article-title":"Innate immunity in tuberculosis: host defense vs pathogen\nevasion","volume":"14","author":"Liu","year":"2017","journal-title":"Cell. 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Immunol"},{"issue":"6","key":"2026100909102391900_cit4","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.chom.2015.05.003","article-title":"Mycobacterium\ntuberculosis differentially\nactivates cGAS- and inflammasome-dependent intracellular immune responses\nthrough ESX-1","volume":"17","author":"Wassermann","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"6","key":"2026100909102391900_cit5","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.chom.2015.05.004","article-title":"The cytosolic sensor\ncGAS detects\nMycobacterium tuberculosis DNA to induce type I Interferons and activate\nautophagy","volume":"17","author":"Watson","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"7","key":"2026100909102391900_cit6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000500","article-title":"NOD2, RIP2\nand IRF5 play a critical role in the type I interferon response to\nMycobacterium tuberculosis","volume":"5","author":"Pandey","year":"2009","journal-title":"PLoS Pathog"},{"issue":"6","key":"2026100909102391900_cit7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067277","article-title":"Mycobacterium\ntuberculosis strains are differentially recognized by TLRs with an\nimpact on the immune response","volume":"8","author":"Carmona","year":"2013","journal-title":"PLoS One"},{"issue":"214","key":"2026100909102391900_cit8","doi-asserted-by":"publisher","first-page":"ra20","DOI":"10.1126\/scisignal.2002521","article-title":"STING specifies\nIRF3 phosphorylation by TBK1 in the\ncytosolic DNA signaling pathway","volume":"5","author":"Tanaka","year":"2012","journal-title":"Sci. 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Proteomics"},{"issue":"18","key":"2026100909102391900_cit25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw625","article-title":"Investigating\nessential gene function\nin Mycobacterium tuberculosis using an efficient\nCRISPR interference system","volume":"44","author":"Singh","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"2026100909102391900_cit26","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.4049\/jimmunol.1801303","article-title":"Mycobacterium tuberculosis inhibits autocrine Type I IFN signaling to increase\nintracellular survival","volume":"202","author":"Banks","year":"2019","journal-title":"J. Immunol"},{"issue":"9","key":"2026100909102391900_cit27","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01957-21","article-title":"The A137R\nprotein of African Swine Fever Virus inhibits Type I Interferon production\nvia the autophagy-mediated lysosomal degradation of TBK1","volume":"96","author":"Sun","year":"2022","journal-title":"J. Virol"},{"issue":"5","key":"2026100909102391900_cit28","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00228-23","article-title":"Combinational deletions of MGF110\u20139L and MGF505\u20137R\ngenes from the African Swine Fever Virus inhibit TBK1 degradation\nby an autophagy activator PIK3C2B to promote Type I Interferon production","volume":"97","author":"Zhu","year":"2023","journal-title":"J. Virol"},{"issue":"6","key":"2026100909102391900_cit29","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202201856R","article-title":"Deletion\nof MGF-110-9L gene from African swine fever virus weakens autophagic\ndegradation of TBK1 as a mechanism for enhancing type I interferon\nproduction","volume":"37","author":"Ren","year":"2023","journal-title":"Faseb J"},{"issue":"7","key":"2026100909102391900_cit30","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1093\/abbs\/gmaa051","article-title":"TBK1, a central kinase\nin innate\nimmune sensing of nucleic acids and beyond","volume":"52","author":"Zhou","year":"2020","journal-title":"Acta Biochim. Biophys. Sin"},{"issue":"9","key":"2026100909102391900_cit31","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/j.chom.2024.07.003","article-title":"A human commensal-pathogenic fungus suppresses\nhost immunity via\ntargeting TBK1","volume":"32","author":"Luo","year":"2024","journal-title":"Cell Host Microbe"},{"issue":"11","key":"2026100909102391900_cit32","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.4049\/jimmunol.2100320","article-title":"African Swine\nFever Virus pI215L negatively regulates cGAS-STING signaling pathway\nthrough recruiting RNF138 to inhibit K63-linked Ubiquitination of\nTBK1","volume":"207","author":"Huang","year":"2021","journal-title":"J. Immunol"},{"issue":"11","key":"2026100909102391900_cit33","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1016\/j.chom.2023.09.010","article-title":"Mycobacterium tuberculosis suppresses\nhost DNA repair to boost its intracellular survival","volume":"31","author":"Liu","year":"2023","journal-title":"Cell Host Microbe"},{"issue":"5","key":"2026100909102391900_cit34","doi-asserted-by":"publisher","first-page":"109807","DOI":"10.1016\/j.isci.2024.109807","article-title":"Mycobacterial CpsA activates type I IFN signaling in\nmacrophages via cGAS-mediated pathway","volume":"27","author":"Ding","year":"2024","journal-title":"iScience"},{"issue":"6","key":"2026100909102391900_cit35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011482","article-title":"LygA retention on the\nsurface of Listeria monocytogenes via its interaction\nwith wall teichoic acid modulates bacterial homeostasis and virulence","volume":"19","author":"Yao","year":"2023","journal-title":"PLoS Pathog"},{"key":"2026100909102391900_cit36","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/ni.2667","article-title":"Structural\nbasis of a unique interferon-\u03b2 signaling axis mediated via the\nreceptor IFNAR1","volume":"14","author":"de Weerd","year":"2013","journal-title":"Nat. Immunol"}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.6c00364","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/10\/3385\/68593759\/acsinfecdis.6c00364.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/10\/3385\/68593759\/acsinfecdis.6c00364.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:31:36Z","timestamp":1791552696000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/12\/10\/3385\/5435045\/Mycobacterium-tuberculosis-Rv3248c-Inhibits-Type-I"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,22]]},"published-print":{"date-parts":[[2026,10,9]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.6c00364","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]}}}