Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers
IntroductionSpontaneous 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 th...
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| Format: | Article |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1017164/full |
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| author | Enrique Martin-Gayo Enrique Martin-Gayo Ce Gao Ce Gao Marta Calvet-Mirabent Zhengyu Ouyang Zhengyu Ouyang Mathias Lichterfeld Mathias Lichterfeld Xu G. Yu Xu G. Yu |
| author_facet | Enrique Martin-Gayo Enrique Martin-Gayo Ce Gao Ce Gao Marta Calvet-Mirabent Zhengyu Ouyang Zhengyu Ouyang Mathias Lichterfeld Mathias Lichterfeld Xu G. Yu Xu G. Yu |
| author_sort | Enrique Martin-Gayo |
| collection | DOAJ |
| description | IntroductionSpontaneous 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 methodsHere, 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.DiscussionTogether, 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. |
| first_indexed | 2024-04-11T13:29:20Z |
| format | Article |
| id | doaj.art-d0993bba3c584d35905b779477dfc941 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T13:29:20Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d0993bba3c584d35905b779477dfc9412022-12-22T04:21:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10171641017164Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllersEnrique Martin-Gayo0Enrique Martin-Gayo1Ce Gao2Ce Gao3Marta Calvet-Mirabent4Zhengyu Ouyang5Zhengyu Ouyang6Mathias Lichterfeld7Mathias Lichterfeld8Xu G. Yu9Xu G. Yu10Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Massachusetts General Hospital, Cambridge, MA, United StatesUniversidad Autónoma de Madrid, Immunology Unit, Hospital Universitario de la Princesa, Madrid, SpainRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Massachusetts General Hospital, Cambridge, MA, United StatesInfectious Disease Divisions, Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, MA, United StatesUniversidad Autónoma de Madrid, Immunology Unit, Hospital Universitario de la Princesa, Madrid, SpainRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Massachusetts General Hospital, Cambridge, MA, United StatesInfectious Disease Divisions, Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Massachusetts General Hospital, Cambridge, MA, United StatesInfectious Disease Divisions, Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Massachusetts General Hospital, Cambridge, MA, United StatesInfectious Disease Divisions, Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, MA, United StatesIntroductionSpontaneous 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 methodsHere, 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.DiscussionTogether, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1017164/fullHIV-1innate immunitymyeloid dendritic cellsDNA sensorRNA sensor |
| spellingShingle | Enrique Martin-Gayo Enrique Martin-Gayo Ce Gao Ce Gao Marta Calvet-Mirabent Zhengyu Ouyang Zhengyu Ouyang Mathias Lichterfeld Mathias Lichterfeld Xu G. Yu Xu G. Yu Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers Frontiers in Immunology HIV-1 innate immunity myeloid dendritic cells DNA sensor RNA sensor |
| title | Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers |
| title_full | Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers |
| title_fullStr | Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers |
| title_full_unstemmed | Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers |
| title_short | Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers |
| title_sort | cooperation between cgas and rig i sensing pathways enables improved innate recognition of hiv 1 by myeloid dendritic cells in elite controllers |
| topic | HIV-1 innate immunity myeloid dendritic cells DNA sensor RNA sensor |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1017164/full |
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