biostudies-literatureTriana SDeutsche Forschungsgemeinschaft (DFG)Bundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftEuropean Research CouncilBundesministerium für Bildung und Forschung (BMBF)DAADe10232https://www.ebi.ac.uk/biostudies/studies/S-EPMC8077299biostudies-literatureUnknown17(4)Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS-CoV-2 and, interestingly, found the lack of positive correlation between susceptibility to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon. These findings reveal that SARS-CoV-2 curtails the immune response and highlights the gut as a pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.Molecular systems biologySingle-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut.PMC807729941607209127298381301KI20198A24024566077308941508955327800197201KI20239B57440921Boulant SMetz-Zumaran CHerrmann CSharma AKShahraz MSchraivogel DGschwind ARAlexandrov TRamirez CSteinmetz LMStanifer MLTriana SDoldan PKee CfalseSingle-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut.Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS-CoV-2 and, interestingly, found the lack of positive correlation between susceptibility to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon. These findings reveal that SARS-CoV-2 curtails the immune response and highlights the gut as a pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.2021-01-01T00:00:00Z2021 Apr2026-05-08T21:28:40.424Z2022-02-10T14:47:39.862ZS-EPMC80772993390465110.15252/msb.202110232