First Author | Salvi V | Year | 2021 |
Journal | JCI Insight | Volume | 6 |
Issue | 18 | PubMed ID | 34375313 |
Mgi Jnum | J:313336 | Mgi Id | MGI:6787434 |
Doi | 10.1172/jci.insight.150542 | Citation | Salvi V, et al. (2021) SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8. JCI Insight 6(18):e150542 |
abstractText | The inflammatory and IFN pathways of innate immunity play a key role in the resistance and pathogenesis of coronavirus disease 2019 (COVID-19). Innate sensors and SARS-CoV-2-associated molecular patterns (SAMPs) remain to be completely defined. Here, we identified single-stranded RNA (ssRNA) fragments from the SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and function, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream of these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identified TLR7/8 as a crucial cellular sensor of ssRNAs encoded by SARS-CoV-2 involved in host resistance and the disease pathogenesis of COVID-19. |