{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:20:15Z","timestamp":1790850015945,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by which Mycobacterium tuberculosis (Mtb), the agent of TB in humans, worsens HIV-1 pathogenesis still need to be fully elucidated. Recently, we showed that HIV-1 infection and spread are exacerbated in macrophages exposed to TB-associated microenvironments. Transcriptomic analysis of macrophages conditioned with medium of Mtb-infected human macrophages (cmMTB) revealed an up-regulation of the typeI interferon (IFN-I) pathway, characterized by the overexpression of IFN-inducible genes. Historically, IFN-I are well known for their antiviral functions, but our previous work showed that this is not the case in the context of coinfection with HIV-1. Here, we show that the IFN-I response signature in cmMTB-treated macrophages matches the one observed in the blood of active TB patients, and depends on the timing of incubation with cmMTB. This suggests that the timing of macrophage's exposure to IFN-I can impact their capacity to control HIV-1 infection. Strikingly, we found that cmMTB-treated macrophages are hyporesponsive to extrastimulation with exogenous IFN-I, used to mimic HIV-1 infection. Yet, depleting STAT1 by gene silencing to block the IFN-I signaling pathway reduced TB-induced exacerbation of HIV-1 infection. Altogether, by aiming to understand why TB-derived IFN-I preexposure of macrophages did not induce antiviral immunity against HIV-1, we demonstrated that these cells are hyporesponsive to exogenous IFN-I, a phenomenon that prevents macrophage activation against HIV-1.<\/jats:p>","DOI":"10.1002\/jlb.4ma0422-730r","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T12:12:45Z","timestamp":1652962365000},"page":"1329-1342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dysregulation of the IFN-I signaling pathway by<i>Mycobacterium tuberculosis<\/i>leads to exacerbation of HIV-1 infection of macrophages"],"prefix":"10.1093","volume":"112","author":[{"given":"Maeva","family":"Dupont","sequence":"first","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"},{"name":"The Sir William Dunn School of Pathology, The University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Rousset","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"Department of Infectious and Tropical Diseases, Toulouse University Hospital , Toulouse Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thien-Phong Vu","family":"Manh","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, INSERM, CIML , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Catherine","family":"Monard","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Pingris","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanti","family":"Souriant","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00ef","family":"Vahlas","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e0s","family":"Velez","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Poincloux","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"I","given":"Isabelle","family":"Maridonneau-Parini","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Neyrolles","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geanncarlo","family":"Lugo-Villarino","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"V\u00e9rollet","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, IPBS, Universit\u00e9 de Toulouse, CNRS, UPS , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Toulouse, France"},{"name":"International Research Project (IRP) CNRS \u201cMAC-TB\/HIV\u201d , Buenos Aires, 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