tetano
Editor, Senior Moderator
JCI Insight
. 2021 Aug 10;150542.
doi: 10.1172/jci.insight.150542. Online ahead of print.
SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8
Valentina Salvi[SUP] 1 [/SUP], Hoang Oanh Nguyen[SUP] 1 [/SUP], Francesca Sozio[SUP] 1 [/SUP], Tiziana Schioppa[SUP] 1 [/SUP], Carolina Gaudenzi[SUP] 1 [/SUP], Mattia Laffranchi[SUP] 1 [/SUP], Patrizia Scapini[SUP] 2 [/SUP], Mauro Passari[SUP] 1 [/SUP], Ilaria Barbazza[SUP] 1 [/SUP], Laura Tiberio[SUP] 1 [/SUP], Nicola Tamassia[SUP] 2 [/SUP], Cecilia Garlanda[SUP] 3 [/SUP], Annalisa Del Prete[SUP] 1 [/SUP], Marco Antonio Cassatella[SUP] 2 [/SUP], Alberto Mantovani[SUP] 3 [/SUP], Silvano Sozzani[SUP] 4 [/SUP], Daniela Bosisio[SUP] 1 [/SUP]
Affiliations
Abstract
The inflammatory and IFN pathways of innate immunity play a key role in both 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 identify single-stranded RNA (ssRNA) fragments from 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 functions, 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 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 identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.
Keywords: Cytokines; Dendritic cells; Immunology; Innate immunity.
. 2021 Aug 10;150542.
doi: 10.1172/jci.insight.150542. Online ahead of print.
SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8
Valentina Salvi[SUP] 1 [/SUP], Hoang Oanh Nguyen[SUP] 1 [/SUP], Francesca Sozio[SUP] 1 [/SUP], Tiziana Schioppa[SUP] 1 [/SUP], Carolina Gaudenzi[SUP] 1 [/SUP], Mattia Laffranchi[SUP] 1 [/SUP], Patrizia Scapini[SUP] 2 [/SUP], Mauro Passari[SUP] 1 [/SUP], Ilaria Barbazza[SUP] 1 [/SUP], Laura Tiberio[SUP] 1 [/SUP], Nicola Tamassia[SUP] 2 [/SUP], Cecilia Garlanda[SUP] 3 [/SUP], Annalisa Del Prete[SUP] 1 [/SUP], Marco Antonio Cassatella[SUP] 2 [/SUP], Alberto Mantovani[SUP] 3 [/SUP], Silvano Sozzani[SUP] 4 [/SUP], Daniela Bosisio[SUP] 1 [/SUP]
Affiliations
- PMID: 34375313
- DOI: 10.1172/jci.insight.150542
Abstract
The inflammatory and IFN pathways of innate immunity play a key role in both 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 identify single-stranded RNA (ssRNA) fragments from 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 functions, 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 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 identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.
Keywords: Cytokines; Dendritic cells; Immunology; Innate immunity.