1. Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans
- Author
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O’neill, Mary, Quach, Hélène, Pothlichet, Julien, Aquino, Yann, Bisiaux, Aurélie, Zidane, Nora, Deschamps, Matthieu, Libri, Valentina, Hasan, Milena, Zhang, Shen-Ying, Zhang, Qian, Matuozzo, Daniela, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Naffakh, Nadia, Rotival, Maxime, Quintana-Murci, Lluis, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Diaccurate SAS, Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], Howard Hughes Medical Institute (HHMI), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Collège de France (CdF (institution)), This work was supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10- LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), the Fondation de France (n°00106080), and the Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214). MO’N was supported by a European Molecular Biology Organization long-term fellowship (ALTF 229-2017)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Éco-Anthropologie (EA), Collège Doctoral, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), Collège de France - Chaire Génomique humaine et évolution, European Project: ALTF 229-2017, Gestionnaire, Hal Sorbonne Université, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, and European Molecular Biology Organization long-term fellowship - ALTF 229-2017 - INCOMING
- Subjects
Adult ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Immunology ,population ,Black People ,GPI-Linked Proteins ,Monocytes ,influenza virus ,White People ,transcriptomics ,Young Adult ,Hypothesis and Theory ,Influenza, Human ,Immunology and Allergy ,Humans ,Sequence Analysis, RNA ,ancestry ,Receptors, IgG ,Middle Aged ,single-cell ‘omics ,Influenza A virus ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cytokines ,single-cell 'omics ,Single-Cell Analysis ,Ribosomes - Abstract
International audience; There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use single-cell RNA-sequencing to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. We show widespread inter-individual variability in the percentage of IAV-infected monocytes. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3 , MX1 and OAS3 . Upon IAV challenge, we find that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. We also uncover a stronger resistance of CD16 + monocytes to IAV infection, together with CD16 + -specific mRNA expression of IL6 and TNF in response to IAV. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16 + monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Based on these data, we hypothesize that higher basal monocyte activation, driven by environmental factors and/or weak-effect genetic variants, underlies the lower cellular susceptibility to IAV infection of individuals of African ancestry relative to those of European ancestry. Further studies are now required to investigate how such cellular differences in IAV susceptibility translate into population differences in clinical outcomes and susceptibility to severe influenza.
- Published
- 2021
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