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.

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8 / Salvi, V.; Nguyen, H. O.; Sozio, F.; Schioppa, T.; Gaudenzi, C.; Laffranchi, M.; Scapini, P.; Passari, M.; Barbazza, I.; Tiberio, L.; Tamassia, N.; Garlanda, C.; Del Prete, A.; Cassatella, M. A.; Mantovani, A.; Sozzani, S.; Bosisio, D.. - In: JCI INSIGHT. - ISSN 2379-3708. - 6:18(2021). [10.1172/jci.insight.150542]

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8

Sozio F.;Laffranchi M.;Sozzani S.
Penultimo
Writing – Original Draft Preparation
;
2021

Abstract

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.
2021
cytokines; dendritic cells; immunology; innate immunity; COVID-19; humans; lung; RNA, viral; SARS-CoV-2; toll-like receptor 7
01 Pubblicazione su rivista::01a Articolo in rivista
SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8 / Salvi, V.; Nguyen, H. O.; Sozio, F.; Schioppa, T.; Gaudenzi, C.; Laffranchi, M.; Scapini, P.; Passari, M.; Barbazza, I.; Tiberio, L.; Tamassia, N.; Garlanda, C.; Del Prete, A.; Cassatella, M. A.; Mantovani, A.; Sozzani, S.; Bosisio, D.. - In: JCI INSIGHT. - ISSN 2379-3708. - 6:18(2021). [10.1172/jci.insight.150542]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1613610
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