Thorne, LG; Reuschl, A-K; Zuliani-Alvarez, L; Whelan, MVX; Turner, J; Noursadeghi, M; Jolly, C; Thorne, LG; Reuschl, A-K; Zuliani-Alvarez, L; Whelan, MVX; Turner, J; Noursadeghi, M; Jolly, C; Towers, GJ; - view fewer (2021) SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation. EMBO Journal , Article e107826. 10.15252/embj.2021107826. (In press).

Preview

Text ThorneEMBOJ.pdf - Accepted Version Download (10MB) | Preview

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 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.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as XMLJSONCSV

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item