Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans
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 het...
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2021
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oai:doaj.org-article:0a9bfd47b5d7452aa289e2635dc3985a2021-12-01T13:36:50ZSingle-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans1664-322410.3389/fimmu.2021.768189https://doaj.org/article/0a9bfd47b5d7452aa289e2635dc3985a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.768189/fullhttps://doaj.org/toc/1664-3224There 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.Mary B. O’NeillHélène QuachJulien PothlichetYann AquinoYann AquinoAurélie BisiauxNora ZidaneMatthieu DeschampsValentina LibriMilena HasanShen-Ying ZhangShen-Ying ZhangShen-Ying ZhangQian ZhangQian ZhangQian ZhangDaniela MatuozzoDaniela MatuozzoAurélie CobatAurélie CobatLaurent AbelLaurent AbelLaurent AbelJean-Laurent CasanovaJean-Laurent CasanovaJean-Laurent CasanovaJean-Laurent CasanovaNadia NaffakhMaxime RotivalLluis Quintana-MurciLluis Quintana-MurciFrontiers Media S.A.articleMonocytessingle-cell ‘omicstranscriptomicsancestrypopulationinfluenza virusImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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Monocytes single-cell ‘omics transcriptomics ancestry population influenza virus Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
Monocytes single-cell ‘omics transcriptomics ancestry population influenza virus Immunologic diseases. Allergy RC581-607 Mary B. O’Neill Hélène Quach Julien Pothlichet Yann Aquino Yann Aquino Aurélie Bisiaux Nora Zidane Matthieu Deschamps Valentina Libri Milena Hasan Shen-Ying Zhang Shen-Ying Zhang Shen-Ying Zhang Qian Zhang Qian Zhang Qian Zhang Daniela Matuozzo Daniela Matuozzo Aurélie Cobat Aurélie Cobat Laurent Abel Laurent Abel Laurent Abel Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Nadia Naffakh Maxime Rotival Lluis Quintana-Murci Lluis Quintana-Murci Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans |
| description |
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. |
| format |
article |
| author |
Mary B. O’Neill Hélène Quach Julien Pothlichet Yann Aquino Yann Aquino Aurélie Bisiaux Nora Zidane Matthieu Deschamps Valentina Libri Milena Hasan Shen-Ying Zhang Shen-Ying Zhang Shen-Ying Zhang Qian Zhang Qian Zhang Qian Zhang Daniela Matuozzo Daniela Matuozzo Aurélie Cobat Aurélie Cobat Laurent Abel Laurent Abel Laurent Abel Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Nadia Naffakh Maxime Rotival Lluis Quintana-Murci Lluis Quintana-Murci |
| author_facet |
Mary B. O’Neill Hélène Quach Julien Pothlichet Yann Aquino Yann Aquino Aurélie Bisiaux Nora Zidane Matthieu Deschamps Valentina Libri Milena Hasan Shen-Ying Zhang Shen-Ying Zhang Shen-Ying Zhang Qian Zhang Qian Zhang Qian Zhang Daniela Matuozzo Daniela Matuozzo Aurélie Cobat Aurélie Cobat Laurent Abel Laurent Abel Laurent Abel Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Nadia Naffakh Maxime Rotival Lluis Quintana-Murci Lluis Quintana-Murci |
| author_sort |
Mary B. O’Neill |
| title |
Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans |
| title_short |
Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans |
| title_full |
Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans |
| title_fullStr |
Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans |
| title_full_unstemmed |
Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans |
| title_sort |
single-cell and bulk rna-sequencing reveal differences in monocyte susceptibility to influenza a virus infection between africans and europeans |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/0a9bfd47b5d7452aa289e2635dc3985a |
| work_keys_str_mv |
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