Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells
Summary: Sensing of incoming viruses is a pivotal task of dendritic cells (DCs). Human primary blood DCs encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of the blood Axl+DC subset, endowed with unique capacities to bind, replicate,...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000962 |
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| author | Flavien Brouiller Francesca Nadalin Pierre-Emmanuel Bonté Ouardia Ait-Mohamed Constance Delaugerre Jean-Daniel Lelièvre Florent Ginhoux Nicolas Ruffin Philippe Benaroch |
| author_facet | Flavien Brouiller Francesca Nadalin Pierre-Emmanuel Bonté Ouardia Ait-Mohamed Constance Delaugerre Jean-Daniel Lelièvre Florent Ginhoux Nicolas Ruffin Philippe Benaroch |
| author_sort | Flavien Brouiller |
| collection | DOAJ |
| description | Summary: Sensing of incoming viruses is a pivotal task of dendritic cells (DCs). Human primary blood DCs encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of the blood Axl+DC subset, endowed with unique capacities to bind, replicate, and transmit HIV-1 prompted us to evaluate its anti-viral response. We demonstrate that HIV-1 induced two main broad and intense transcriptional programs in different Axl+DCs potentially induced by different sensors; an NF-κB-mediated program that led to DC maturation and efficient CD4+ T cell activation, and a program mediated by STAT1/2 that activated type I IFN and ISG responses. These responses were absent from cDC2 exposed to HIV-1 except when viral replication was allowed. Finally, Axl+DCs actively replicating HIV-1 identified by quantification of viral transcripts exhibited a mixed NF-κB/ISG innate response. Our results suggest that the route of HIV-1 entry may dictate different innate sensing pathways by DCs. |
| first_indexed | 2024-04-10T09:31:05Z |
| format | Article |
| id | doaj.art-89b4eaaa143f4e2ca45bc00c0d76cba0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:05Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-89b4eaaa143f4e2ca45bc00c0d76cba02023-02-19T04:26:57ZengElsevieriScience2589-00422023-02-01262106019Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cellsFlavien Brouiller0Francesca Nadalin1Pierre-Emmanuel Bonté2Ouardia Ait-Mohamed3Constance Delaugerre4Jean-Daniel Lelièvre5Florent Ginhoux6Nicolas Ruffin7Philippe Benaroch8Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, FranceInstitut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, FranceInstitut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, FranceInstitut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, FranceLaboratoire de Virologie, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM U944, Université de Paris, Paris, FranceVaccine Research Institute, Institut National de la Santé et de la Recherche médicale (INSERM), Assistance Publique Hôpitaux de Paris (APHP), Hôpital H. Mondor, Créteil, FranceSingapore Immunology Network (SIgN), A∗STAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore 169856, SingaporeInstitut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France; Corresponding authorInstitut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France; Corresponding authorSummary: Sensing of incoming viruses is a pivotal task of dendritic cells (DCs). Human primary blood DCs encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of the blood Axl+DC subset, endowed with unique capacities to bind, replicate, and transmit HIV-1 prompted us to evaluate its anti-viral response. We demonstrate that HIV-1 induced two main broad and intense transcriptional programs in different Axl+DCs potentially induced by different sensors; an NF-κB-mediated program that led to DC maturation and efficient CD4+ T cell activation, and a program mediated by STAT1/2 that activated type I IFN and ISG responses. These responses were absent from cDC2 exposed to HIV-1 except when viral replication was allowed. Finally, Axl+DCs actively replicating HIV-1 identified by quantification of viral transcripts exhibited a mixed NF-κB/ISG innate response. Our results suggest that the route of HIV-1 entry may dictate different innate sensing pathways by DCs.http://www.sciencedirect.com/science/article/pii/S2589004223000962Biological sciencesClinical microbiologyMicrobiologyMolecular biologyTranscriptomics |
| spellingShingle | Flavien Brouiller Francesca Nadalin Pierre-Emmanuel Bonté Ouardia Ait-Mohamed Constance Delaugerre Jean-Daniel Lelièvre Florent Ginhoux Nicolas Ruffin Philippe Benaroch Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells iScience Biological sciences Clinical microbiology Microbiology Molecular biology Transcriptomics |
| title | Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells |
| title_full | Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells |
| title_fullStr | Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells |
| title_full_unstemmed | Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells |
| title_short | Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells |
| title_sort | single cell rna seq analysis reveals dual sensing of hiv 1 in blood axl dendritic cells |
| topic | Biological sciences Clinical microbiology Microbiology Molecular biology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000962 |
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