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Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl(+) dendritic cells
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 tra...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971904/ https://www.ncbi.nlm.nih.gov/pubmed/36866043 http://dx.doi.org/10.1016/j.isci.2023.106019 |
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author | Brouiller, Flavien Nadalin, Francesca Bonté, Pierre-Emmanuel Ait-Mohamed, Ouardia Delaugerre, Constance Lelièvre, Jean-Daniel Ginhoux, Florent Ruffin, Nicolas Benaroch, Philippe |
author_facet | Brouiller, Flavien Nadalin, Francesca Bonté, Pierre-Emmanuel Ait-Mohamed, Ouardia Delaugerre, Constance Lelièvre, Jean-Daniel Ginhoux, Florent Ruffin, Nicolas Benaroch, Philippe |
author_sort | Brouiller, Flavien |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9971904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99719042023-03-01 Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl(+) dendritic cells Brouiller, Flavien Nadalin, Francesca Bonté, Pierre-Emmanuel Ait-Mohamed, Ouardia Delaugerre, Constance Lelièvre, Jean-Daniel Ginhoux, Florent Ruffin, Nicolas Benaroch, Philippe iScience Article 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. Elsevier 2023-01-20 /pmc/articles/PMC9971904/ /pubmed/36866043 http://dx.doi.org/10.1016/j.isci.2023.106019 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Brouiller, Flavien Nadalin, Francesca Bonté, Pierre-Emmanuel Ait-Mohamed, Ouardia Delaugerre, Constance Lelièvre, Jean-Daniel Ginhoux, Florent Ruffin, Nicolas Benaroch, Philippe Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl(+) dendritic cells |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971904/ https://www.ncbi.nlm.nih.gov/pubmed/36866043 http://dx.doi.org/10.1016/j.isci.2023.106019 |
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