Impact of Sting Pathway in Inflammation and Covid-19 Pathogenesis

Abstract

The recent encounter by Sars-Cov2 (COVID-19) presented the need of having stronger immune system as the first line of body’s defense mechanism. Stronger the immune response better will be the pathogen recognition. Better understanding of immune response mechanism and functioning of its components will pave the route for defending against these pathogens. Innate immune defense being non-specific in nature identifies both DNA and RNA viruses as well as other pathogens attacking the body. Presence of foreign nucleic acids bound to the specific pattern recognition receptors (PRRs) which include toll-like receptors (TLRs), cGAS-STING, Nod-like receptors (NLR) and RNA helicase receptors (RIG-1 and MDA5) triggers a signaling cascade. These signaling channels direct to the production of type-1 interferons and other cytokine/chemokine effectors of innate immune system which in turn activate adaptive immune response. STING pathway as a prime innate detector of self and non-self-nucleic acids plays an important role in the development of inflammation followed by type-1 interferon production. COVID-19 being involved with the respiratory failure shows the main characteristic feature of cytokine storm which direct to hyper inflammation. These hyper-inflammatory responses worsen the immune compromised state of the patients which makes this disease as the leading cause of mortality worldwide. Understanding the underline mechanisms involved in and regulating the process of hyper inflammation would provide an effective treatment to reduce the mortalities. Deregulation of STING pathway is involved in various inflammatory diseases that make it a potent target to understand its mechanism of work during viral attack. Many recent studies have further supported the importance of delayed STING signaling in the pathogenesis of COVID-19 during the second phase of this disease. This review mainly focuses on the role of STING in inflammation and its function in our immune system which can be harnessed to tackle the recent pathogeneses of COVID-19.