Abstract
The cytosolic PRRs and Cyclic GMP-AMP synthase (cGAS) attain the capability to detect DNA viruses like, vaccinia virus, HSV1 and HSV2, cytomegalovirus, adenoviruses, human papilloma virus etc and clear them off via IFN I regulations. PRRs can recognize the pathogen associated molecular patterns- PAMPs and self-DNA in the form of damage associated molecular patterns- DAMPs under stressed conditions, when monocytes and macrophages with other immune cells release excessive proinflammatory cytokines. Cytotoxic ssDNA and dsDNA escape from endosome and rupture mitochondrial DNA as well. The cGAS-STING signaling also have the polymorphic role to increase the pathogenesis in case of positive sense RNA virus’s infection (SARSCoV-2), retroviruses and bacterial pathogens. STING protein is primarily present on ER, mitochondrial and Golgi bodies and gets activated through ligands cGAS / or cGAMP (2’-3’-cGAMP). This specific molecular pathway triggers the innate immune response in the cytoplasm and consecutively develop the adaptive immune arm against the pathogens. Activation of cGAS-STING signaling also exerts the antitumor effects via activation of p53 and p16 proteins. TLR9 is expressed on the DCs and B-cells to detect CpG motif of DNA. PRR agonists activate the STING to work effectively on CD4+ and CD8+ cells to establish the sustainable innate & adaptive immune response. STING also harbours the adjuvant properties to release potent immune response in the development of novel therapeutics against cancer, autoimmune and infectious diseases.