SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation Article Swipe
Lucy Thorne
,
Ann‐Kathrin Reuschl
,
Lorena Zuliani‐Alvarez
,
Matthew V. X. Whelan
,
Mahdad Noursadeghi
,
Clare Jolly
,
Greg J. Towers
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.12.23.424169
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.12.23.424169
Summary SARS-CoV-2 infection causes broad-spectrum immunopathological disease, exacerbated by inflammatory co-morbidities. A better understanding of mechanisms underpinning virus-associated inflammation is required to develop effective therapeutics. Here we discover that SARS-CoV-2 replicates rapidly in lung epithelial cells despite triggering a robust innate immune response through activation of cytoplasmic RNA-ensors RIG-I and MDA5. The inflammatory mediators produced during epithelial cell infection can stimulate primary human macrophages to enhance cytokine production and drive cellular activation. Critically, this can be limited by abrogating RNA sensing, or by inhibiting downstream signalling pathways. SARS-CoV-2 further exacerbates the local inflammatory environment when macrophages or epithelial cells are primed with exogenous inflammatory stimuli. We propose that RNA sensing of SARS-CoV-2 in lung epithelium is a key driver of inflammation, the extent of which is influenced by the inflammatory state of the local environment, and that specific inhibition of innate immune pathways may beneficially mitigate inflammation-associated COVID-19. Highlights SARS-CoV-2 activates RNA sensors and consequent inflammatory responses in lung epithelial cells Epithelial RNA sensing responses drive pro-inflammatory macrophage activation Exogenous inflammatory stimuli exacerbate responses to SARS-CoV-2 in both eplithelial cells and macrophages Immunomodulators inhibit RNA sensing responses and consequent macrophage inflammation Graphical Abstract
Related Topics
Concepts
Inflammation
MDA5
Innate immune system
Macrophage
Immune system
Immunology
Biology
RIG-I
RNA
Cytokine
Lung
Cell biology
Medicine
RNA interference
Gene
In vitro
Biochemistry
Internal medicine
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2020.12.23.424169
- https://www.biorxiv.org/content/biorxiv/early/2020/12/23/2020.12.23.424169.full.pdf
- OA Status
- green
- Cited By
- 24
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3117287459
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3117287459Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2020.12.23.424169Digital Object Identifier
- Title
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SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammationWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2020Year of publication
- Publication date
-
2020-12-23Full publication date if available
- Authors
-
Lucy Thorne, Ann‐Kathrin Reuschl, Lorena Zuliani‐Alvarez, Matthew V. X. Whelan, Mahdad Noursadeghi, Clare Jolly, Greg J. TowersList of authors in order
- Landing page
-
https://doi.org/10.1101/2020.12.23.424169Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2020/12/23/2020.12.23.424169.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2020/12/23/2020.12.23.424169.full.pdfDirect OA link when available
- Concepts
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Inflammation, MDA5, Innate immune system, Macrophage, Immune system, Immunology, Biology, RIG-I, RNA, Cytokine, Lung, Cell biology, Medicine, RNA interference, Gene, In vitro, Biochemistry, Internal medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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24Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 8, 2023: 3, 2022: 5, 2021: 7Per-year citation counts (last 5 years)
- References (count)
-
60Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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