Endogenous Nucleic Acid Recognition by RIG-I-Like Receptors and cGAS

The innate immune defense of mammalian hosts relies on its capacity to detect invading pathogens and then directly eliminate them or help guide adaptive immune responses. Recognition of microbial DNA and RNA by pattern recognition receptors (PRRs) is central to the detection of pathogens by initiating cytokine-mediated innate immunity. In contrast, disturbance of this pathogen surveillance system can result in aberrant innate immune activation, leading to proinflammatory or autoimmune diseases. Among the many important PRRs are proteins of the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) family as well as cyclic GMP-AMP synthase (cGAS), which detect viral RNA and DNA, respectively, within the host cell. Intriguingly, recent evidence has shown that "unmasked," misprocessed, or mislocalized host-derived RNA or DNA molecules can also be recognized by RLRs or cGAS, thereby triggering antiviral host defenses or causing inflammation. Here, we review recent advances of endogenous nucleic acid recognition by RLRs and cGAS during viral infection and systemic proinflammatory/autoimmune disorders.