SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation.
EMBO J
; 40(15): e107826, 2021 08 02.
Article
in English
| MEDLINE | ID: covidwho-1261483
ABSTRACT
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 the activation of cytoplasmic RNA sensors 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA, Viral
/
Receptors, Immunologic
/
Epithelial Cells
/
DEAD Box Protein 58
/
Interferon-Induced Helicase, IFIH1
/
SARS-CoV-2
/
COVID-19
/
Macrophages
Limits:
Humans
Language:
English
Journal:
EMBO J
Year:
2021
Document Type:
Article
Affiliation country:
Embj.2021107826
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