Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells

• Published in: iScience Vol. 26; no. 2; p. 106019
• Main Authors: Brouiller, Flavien, Nadalin, Francesca, Bonté, Pierre-Emmanuel, Ait-Mohamed, Ouardia, Delaugerre, Constance, Lelièvre, Jean-Daniel, Ginhoux, Florent, Ruffin, Nicolas, Benaroch, Philippe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.02.2023; Elsevier
• Subjects: Adaptive immunology; Biological sciences; Clinical microbiology; Immunology; Innate immunity; Life Sciences; Medicin och hälsovetenskap; Microbiology; Microbiology and Parasitology; Molecular biology; Transcriptomics; Virology; Biological sciences; Microbiology; Molecular biology; Transcriptomics; Clinical microbiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106019

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. [Display omitted] •Axl+DCs are unique among human blood DC subsets in their response to HIV-1•HIV-1 induces 2 transcriptional programs in Axl+DCs, likely through different sensors•The NF-ΚB-mediated program is RT-independent and activates T cell help functions•The STA1/2 program induces type I IFN and ISG responses through STING activation Biological sciences; Clinical microbiology; Microbiology; Molecular biology; Transcriptomics