Cytosolic sensing of aberrant DNA: arming STING on the endoplasmic reticulum

Detection of pathogen-derived nucleic acids is a general and effective strategy used by the host to perceive the presence of invading microorganisms and initiate an innate immune response. However, inappropriate detection of aberrant self nucleic acids is implicated in the development of autoimmune diseases. Recently, ER-resident stimulator of interferon genes (STING) has been uncovered as a key component in the innate immune response to cytosolic nucleic acids and a direct sensor for bacterial cyclic dinucleotides. The elucidation of STING-mediated signaling will provide insight into host-microbial interactions and contribute to the development of novel strategies for anti-infection therapies.

This review summarizes the cellular and molecular processes of host sensing and responding to microbial or endogenous aberrant DNA species, highlighting the essential function of STING and the corresponding regulatory mechanisms. The authors also attempt to delineate the role for the DNA-sensing signaling during the onset and progression of autoimmune diseases and suggest improvements in the immunogenicity of DNA vaccines.

It is essential to elucidate how the STING-dependent signaling mediates the DNA vaccines action as well as the pathogenesis of autoimmune diseases. The relevant knowledge will greatly benefit the treatment of infectious diseases and identify potential targets for effective drug design.