A central role of stimulator of interferon genes' adaptor protein in defensive immune response.

Abstract

Cytotoxic DNAs, methylation, histones and histones binding proteins are speculated to induce DNA sensors. Under stressed condition, the antigenic patterns, PAMPs and DAMPs, trigger the hyperactive innate response through DNA, DNA-RNA hybrids, oligonucleotides, histones and mtDNA to initiate cGAMP-STING-IFN I cascade. HSV -1&2, HIV, Varicella- Zoster virus, Polyomavirus, Cytomegalovirus, and KSHV negatively regulate the STING-MAVS-TBK-1/1KKE pathway. Implications in STING-PKR-ER regulation often run into causing senescence and organ fibrosis. Post-translational modifications such as, phosphorylation, ubiquitination, SUMOylation, hydrolysis etc. downstream the processing of cGAS-STING that determine the fate of disease prognosis. Self-DNA under normal circumstances is removed through DNase III action; however, its deficiency is the great cause of RA diseases. Regular STING activation in chronic diseases could lead to exacerbate the neurodegenerative disorders due to constant mtDNA leakage. 2' 3' cGAMP or CDN or its associates are being explored as STING agonist therapeutics to treat solid/metastatic tumors to help infiltrate the immune cells, cytokines and chemokines to regulate the protective response. Liposomes, polymer nanoparticles, and cell-derived nanoparticles are also meant to increase the drug efficiency and stability for desired immune response to enhance the IFN I production. This review highlights the implications of cGAMP-STING- IFN I cascade and related pathways involved in the disease prognosis, therapeutics and considering the gaps on different aspects to utilize its greater potential in disease control.