SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation.

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

SUBMITTER: Thorne LG 

PROVIDER: S-EPMC8209947 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature