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 interferons 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. Graphical Abstract Hyper regulation of TLR7/8 pathways during SARS-CoV2 infection increases production of inflammatory mediators but display lower IFN production but potent agonists can induce IFNs and thereby limit SARS-CoV2 replication. ga1
【저자키워드】 COVID-19, SARS-CoV2, IL-6, TLR7, type I interferons, IL-1β, TLR, Toll like Receptor, TLR8, TLR7/8 agonists, TNFα, Tumor necrosis factor alpha, IL-1, interleukin 1, PKR, protein kinase R, MYD88, Myeloid Differentiation primary response protein 88, CD14, cluster of differentiation 14, LBP, lipopolysaccharide binding protein, MD-2, myeloid differentiation protein 2, ST-2, growth stimulation expressed gene 2 or interleukin 1 receptor like 1 (IL1RL1), TIRAP, ‘TIR’ domain containing adaptor protein, IRAK, interleukin 1 receptor associated kinase 1, TOLLIP, toll interacting protein, TRAF, TNF receptor associated factor, TAB, TGFβ activated kinase (MAP3K7) binding protein, TAK1, TGFβ activated kinase 1, SITPEC or ECSIT, ECSIT signaling integrator, MKK, mitogen activated protein kinase, NIK, NF-kappa-beta inducing kinase, MEKK1, MAPK/ERK kinase kinase 1, IKK, inhibitor of nuclear factor kappa B kinase, IκBα, I kappaB alpha, NFκB, nuclear factor kappaB, PPAR, peroxisome proliferator activated receptor alpha, JNK1, JUN N-terminal kinase, ELK-1, ETS like gene 1 tyrosine kinase oncogene, JUN, jun oncogene, IL-12, interleukin 12,