Role of toll-like receptor 7/8 pathways in regulation of interferon response and inflammatory mediators during SARS-CoV2 infection and potential therapeutic options

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is the causative agent of Corona Virus Disease 2019 (COVID-19). Lower production of type I and III interferon and higher levels of inflammatory mediators upon SARS-CoV2 infection contribute to COVID-19 pathogenesis. Optimal interferon production and controlled inflammation are essential to limit COVID-19 pathogenesis. However, the aggravated inflammatory response observed in COVID-19 patients causes severe damage to the host and frequently advances to acute respiratory distress syndrome (ARDS). Toll-like receptor 7 and 8 (TLR7/8) signaling pathways play a central role in regulating induction of interferons (IFNs) and inflammatory mediators in dendritic cells. Controlled inflammation is possible through regulation of TLR mediated response without influencing interferon production to reduce COVID-19 pathogenesis. This review focuses on inflammatory mediators that contribute to pathogenic effects and the role of TLR pathways in the induction of interferon and inflammatory mediators and their contribution to COVID-19 pathogenesis. We conclude that potential TLR7/8 agonists inducing antiviral interferon response and controlling inflammation are important therapeutic options to effectively eliminate SARS-CoV2 induced pathogenesis. Ongoing and future studies may provide additional evidence on their safety and efficacy to treat COVID-19 pathogenesis.

Automated summary

SARS-CoV2 infection leads to decreased interferon production and aggravated inflammation, contributing to COVID-19 pathogenesis. Controlling inflammation without affecting interferon production can reduce the severity of COVID-19.