Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells
Flavien Brouiller,
Francesca Nadalin,
Pierre-Emmanuel Bonté,
Ouardia Ait-Mohamed,
Constance Delaugerre,
Jean-Daniel Lelièvre,
Florent Ginhoux,
Nicolas Ruffin,
Philippe Benaroch
Affiliations
Flavien Brouiller
Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France
Francesca Nadalin
Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France
Pierre-Emmanuel Bonté
Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France
Ouardia Ait-Mohamed
Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France
Constance Delaugerre
Laboratoire de Virologie, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM U944, Université de Paris, Paris, France
Jean-Daniel Lelièvre
Vaccine Research Institute, Institut National de la Santé et de la Recherche médicale (INSERM), Assistance Publique Hôpitaux de Paris (APHP), Hôpital H. Mondor, Créteil, France
Florent Ginhoux
Singapore 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, Singapore
Nicolas Ruffin
Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France; Corresponding author
Philippe Benaroch
Institut Curie, PSL∗ Research University, INSERM U 932, 75005 Paris, France; Corresponding author
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.
