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.
【저자키워드】 immunology, Cytokines, Innate immunity, dendritic cells, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, Pathogenesis, Innate immunity, Th1, cytokine, virus, RNA, Immune cell infiltration, proinflammatory, Viral, SARS-CoV-2 genome, pathway, phenotype, IFN, receptors, cytokine production, cellular, Inflammatory response, Lung inflammation, Inflammatory, Innate, viral genome, mediators, disease pathogenesis, Activation, maturation, accumulation, sequence, TLR7/8, pathogenesis of COVID-19, ssRNA, MYD88, downstream, IFN pathways, Host, single-stranded, IFN pathway, defined, involved, the disease, characterized, activate, activating, molecular pattern, phenotypical, the SARS-CoV-2 genome, 【제목키워드】 Inflammation, Immunity, activate,