Innate immune DNA sensing pathways

Abstract

How the cells triggers the induction of innate immune genes in response to nucleic acids derived from microbes, such as DNA viruses, intracellular bacteria, and parasites, or self DNA, has not been elucidated fully. We have previously shown that an endoplasmic reticulum (ER)-associated multiple transmembrane protein, so-called STING (stimulator of interferon genes), functions as an essential molecules for triggering DNA-mediated gene induction. STING may directly associate with stimulatory ligands, which include DNA, as well as with cyclic dinucleotides (CDNs), which are secreted by intracellular bacteria. After DNA or CDN stimulation, STING traffics with kinase TBK1 in an autophagic signaling complex, from ER to perinuclear endosomal compartments harboring IRF3 and NF-κB. STING may involve in autoinflammatory disease manifested by aberrant self-DNA. Understanding of STING function may conceivably lead to the development of potent adjuvants for vaccine development or conversely therapeutics that could control inflammation aggravated disease.