Innate Immune Signaling and Infectious Disease: STING Signaling. The Toll-Like Receptor (TLR) and Rig-I-Like (RLR) cellular pathways have been shown to play key roles in recognizing microbial infection, predominantly RNA viruses and bacteria, to trigger innate immune signaling and the generation of type I IFN. In 2008 we additionally reported the discovery of an important cellular protein that we referred to as STING (for stimulator of interferon genes) that controlled a new innate immune signaling pathway. This research lead to elucidating how DNA based microbes trigger host defense countermeasures (Ishikawa and Barber, Nature 2008; Ishikawa, Ma and Barber Nature 2009). Essentially, the cytosol is supposed to be devoid of dsDNA species. If dsDNA species are present, then it likely comes from an invading microbe, from damaged mitochondria or from the nucleus of a DNA-damaged cell. In such circumstances, STING signaling activates cytokine production, likely to attract the immune system to the problematic region. STING is a cytosolic sensor for cyclic dinucleotides (CDN’s; such as GMP-GMP, GMP-AMP). CDN’s are generated by intracellular bacteria or via a cellular synthase referred to as cGAS, which generates CDN’s following interaction with cytosolic microbial or self-dsDNA species. Such work, by us and others has demonstrated that transient STING activity is essential for host defense countermeasures following infection by DNA viruses, bacteria and parasites (Ishikawa and Barber, Nature 2008; Ishikawa et al., Nature 2009; Barber G.N., Nature Immunology Reviews, 2015).