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Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut

Abstract 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 transcriptomic...

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Main Authors: Triana, Sergio (Author) , Metz Zumarán, Camila (Author) , Ramirez, Carlos (Author) , Kee, Carmon (Author) , Doldan, Patricio (Author) , Shahraz, Mohammed (Author) , Schraivogel, Daniel (Author) , Gschwind, Andreas R (Author) , Sharma, Ashwini Kumar (Author) , Steinmetz, Lars M (Author) , Herrmann, Carl (Author) , Alexandrov, Theodore (Author) , Boulant, Steeve (Author) , Stanifer, Megan (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Molecular systems biology
Year: 2021, Volume: 17, Issue: 4, Pages: 1-25
ISSN:1744-4292
DOI:10.15252/msb.202110232
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/msb.202110232
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/msb.202110232
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Author Notes:Sergio Triana, Camila Metz-Zumaran, Carlos Ramirez, Carmon Kee, Patricio Doldan, Mohammed Shahraz, Daniel Schraivogel, Andreas R. Gschwind, Ashwini K.Sharma, Lars M. Steinmetz, Carl Herrmann, Theodore Alexandrov, Steeve Boulant & Megan L. Stanifer
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Summary:Abstract 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.
Item Description:Gesehen am 30.06.2021
Physical Description:Online Resource
ISSN:1744-4292
DOI:10.15252/msb.202110232

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