Frontiers in immunology · 2022
Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Martin-Gayo Enrique, Gao Ce, Calvet-Mirabent Marta, Ouyang Zhengyu, Lichterfeld Mathias, Yu Xu G
Аннотация
INTRODUCTION: 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.
RESULTS AND METHODS: 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.
DISCUSSION: 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.
RESULTS AND METHODS: 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.
DISCUSSION: 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.