Differential role of TLR7 signaling in SARS-CoV-2-induced antiviral and inflammatory responses

Abstract Since its emergence in 2019, SARS-CoV-2 has caused significant morbidity and mortality humans. SARS-CoV-2-induced impaired antiviral excessive inflammatory responses drive acute lung injury severe pneumonia. However, the key pattern recognition receptors that elicit effective pathogenic are not well defined. CoVs single-stranded RNA (ssRNA) viruses make double-stranded (dsRNA) intermediates during replication, we assessed pro-inflammatory roles of ssRNA dsRNA mimics mouse macrophages. We show R837-TLR7 signaling induced inflammation, while PolyIC-TLR3/MDA activation robust IFN production. high levels cytokines, using a novel mouse-adapted SARS-COV-2, examined role TLR7 COVID-19 pathogenesis. Our results KO mice were more susceptible to infection as compared WT mice. Further investigation infected lungs showed significantly reduced mRNA interferons (IFNα/β/λ), ISGs (ISG15 CXCL10), several cytokine/chemokines WT. Interestingly, immunolabelling cells isolated from neutrophil count Furthermore, increased correlated with viral titer In summary, our findings conclusively establish is protective infection, despite TLR7-mediated cytokine production, TLR7-induced ISG play host protection.