Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans.
| Title: | Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans. |
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| Authors: | O'Neill MB; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, Centre National de la Recherche Scientifique (CNRS), Paris, France.; Quach H; Muséum National d'Histoire Naturelle, UMR7206, Centre National de la Recherche Scientifique (CNRS), Université de Paris, Paris, France.; Pothlichet J; DIACCURATE, Paris, France.; Aquino Y; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, Centre National de la Recherche Scientifique (CNRS), Paris, France.; Sorbonne Université, Collège doctoral, Paris, France.; Bisiaux A; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, Centre National de la Recherche Scientifique (CNRS), Paris, France.; Zidane N; Biodiversity and Epidemiology of Bacterial Pathogens Unit, Institut Pasteur, Paris, France.; Deschamps M; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, Centre National de la Recherche Scientifique (CNRS), Paris, France.; Libri V; Cytometry and Biomarkers UTechS, Institut Pasteur, Paris, France.; Hasan M; Cytometry and Biomarkers UTechS, Institut Pasteur, Paris, France.; Zhang SY; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, United States.; Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Paris University, Paris, France.; Zhang Q; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, United States.; Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Paris University, Paris, France.; Matuozzo D; Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Paris University, Paris, France.; Cobat A; Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Paris University, Paris, France.; Abel L; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, United States.; Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Paris University, Paris, France.; Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, United States.; Laboratory of Human Genetics of Infectious Diseases, Necker Hospital for Sick Children, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.; Imagine Institute, Paris University, Paris, France.; Howard Hughes Medical Institute, New York, NY, United States.; Naffakh N; RNA Biology of Influenza Virus Unit, Institut Pasteur, Paris, France.; Rotival M; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, Centre National de la Recherche Scientifique (CNRS), Paris, France.; Quintana-Murci L; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, Centre National de la Recherche Scientifique (CNRS), Paris, France.; Chair of Human Genomics and Evolution, Collège de France, Paris, France. |
| Source: | Frontiers in immunology [Front Immunol] 2021 Nov 29; Vol. 12, pp. 768189. Date of Electronic Publication: 2021 Nov 29 (Print Publication: 2021). |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | Influenza A virus* ; Sequence Analysis, RNA* ; Single-Cell Analysis*; Influenza, Human/*ethnology ; Monocytes/*immunology; Cytokines/physiology ; GPI-Linked Proteins/analysis ; Monocytes/virology ; Receptors, IgG/analysis ; Receptors, IgG/genetics ; Ribosomes/physiology ; Adult ; Black People ; Humans ; Middle Aged ; White People ; Young Adult |
| Abstract: | 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.; (Copyright © 2021 O’Neill, Quach, Pothlichet, Aquino, Bisiaux, Zidane, Deschamps, Libri, Hasan, Zhang, Zhang, Matuozzo, Cobat, Abel, Casanova, Naffakh, Rotival and Quintana-Murci.) |
| Competing Interests: | JP was employed by DIACCURATE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Grant Information: | United States HHMI Howard Hughes Medical Institute |
| Contributed Indexing: | Keywords: Monocytes; ancestry; influenza virus; population; single-cell ‘omics; transcriptomics |
| Substance Nomenclature: | 0 (Cytokines); 0 (FCGR3A protein, human); 0 (FCGR3B protein, human); 0 (GPI-Linked Proteins); 0 (Receptors, IgG) |
| Entry Date(s): | Date Created: 20211216 Date Completed: 20220214 Latest Revision: 20221207 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8667309 |
| DOI: | 10.3389/fimmu.2021.768189 |
| PMID: | 34912340 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't