Reduced SARS-CoV-2 infection and altered antiviral transcriptional response in IBD intestinal organoids
Summary IBD is characterized by altered immune reactions and infections are thought to trigger the chronic inflammatory response in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients in COVID-19. We used large and small intestinal organoids from IBD patients and controls to comparatively assess the transcriptional response of the gut epithelium during SARS- CoV-2 infection. Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD likely counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and an induction of IL-1β despite overall lower viral loads suggestive of increased epithelial stress in this IBD phenotype. Altogether our analysis shows that IBD epithelia are not more prone to SARS-CoV-2 infection but epithelia from ulcerative colitis and Crohn’s disease exhibit specific differences which might explain the differing COVID-19 outcomes between IBD phenotypes..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 09. Juni Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jelusic, Barbara [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.06.05.23290961 |
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| PPN (Katalog-ID): |
XBI039800008 |
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| 245 | 1 | 0 | |a Reduced SARS-CoV-2 infection and altered antiviral transcriptional response in IBD intestinal organoids |
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| 520 | |a Summary IBD is characterized by altered immune reactions and infections are thought to trigger the chronic inflammatory response in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients in COVID-19. We used large and small intestinal organoids from IBD patients and controls to comparatively assess the transcriptional response of the gut epithelium during SARS- CoV-2 infection. Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD likely counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and an induction of IL-1β despite overall lower viral loads suggestive of increased epithelial stress in this IBD phenotype. Altogether our analysis shows that IBD epithelia are not more prone to SARS-CoV-2 infection but epithelia from ulcerative colitis and Crohn’s disease exhibit specific differences which might explain the differing COVID-19 outcomes between IBD phenotypes. | ||
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| 700 | 1 | |a Watschinger, Christina |4 aut | |
| 700 | 1 | |a Wolfgruber, Stella |4 aut | |
| 700 | 1 | |a Anthofer, Margit |4 aut | |
| 700 | 1 | |a Ehman, Sandra |4 aut | |
| 700 | 1 | |a Klages, Sven |4 aut | |
| 700 | 1 | |a Zatloukal, Kurt |4 aut | |
| 700 | 1 | |a Timmermann, Bernd |4 aut | |
| 700 | 1 | |a Moschen, Alexander |4 aut | |
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