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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Spontaneous control of HIV-1 replication in the absence of anti-retroviral therapy (ART) naturally occurs in a small proportion of HIV-1-infected individuals known as elite controllers (EC), likely as a result of improved innate and adaptive immune mechanisms. Previous studies suggest that enhanced cytosolic immune recognition of HIV-1 reverse transcripts in conventional dendritic cells (mDC) from EC enables effective induction of antiviral effector T cell responses. However, the specific molecular circuits responsible for such improved innate recognition of HIV-1 in mDC from these individuals remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and methods<\/jats:title><jats:p>Here, we identified a subpopulation of EC whose mDC displayed higher baseline abilities to respond to intracellular HIV-1 dsDNA stimulation. A computational analysis of transcriptional signatures from such high responder EC, combined with functional studies, suggested cytosolic recognition of HIV-1 dsDNA by cGAS, combined with sensing of viral mRNA by RIG-I after polymerase III-mediated HIV-1 DNA transcription.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Together, our work identifies collaborative networks of innate sensing pathways that enhance cell-intrinsic abilities of mDC to induce antiviral innate responses against HIV-1; these observations might be useful for the therapeutic induction of effective antiviral immune responses.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1017164","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T06:38:25Z","timestamp":1670395105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers"],"prefix":"10.3389","volume":"13","author":[{"given":"Enrique","family":"Martin-Gayo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Calvet-Mirabent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyu","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Lichterfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu 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