Innate immune nucleic acid sensors

Innate immune nucleic acid sensors are a diverse group of pattern recognition receptors (PRRs) that detect foreign or misplaced genomic material, such as viral RNA or cytosolic DNA, to initiate protective immune responses (Frontiers in Immunology, 2017). This class includes endosomal receptors like Toll-like receptors (TLR3, TLR7, TLR8, TLR9) and cytosolic sensors such as cyclic GMP-AMP synthase (cGAS), RIG-I-like receptors (RIG-I, MDA5), and AIM2-like receptors (NIH, 2020). Upon binding to their respective nucleic acid ligands, these sensors trigger signaling cascades that lead to the production of type I interferons and proinflammatory cytokines, as well as the activation of programmed cell death pathways like pyroptosis (MDPI, 2025). While essential for defending against viral and bacterial infections, dysregulation or aberrant sensing of self-nucleic acids is a primary driver of autoimmune and autoinflammatory diseases, such as systemic lupus erythematosus and Aicardi-Goutières syndrome (Frontiers in Immunology, 2023). In oncology, agonists of these sensors are being developed to enhance antitumor immunity by turning cold tumors hot, while inhibitors are being explored to treat chronic inflammatory conditions (NIH, 2020). Therapeutic strategies targeting these sensors include small-molecule agonists for cancer vaccines and antagonists for autoimmune therapy (ResearchGate, 2020).

Other names

Nucleic acid sensorsPattern recognition receptors for nucleic acidsDNA sensorsRNA sensorsCytosolic nucleic acid sensors

Agonists activate sensors to induce type I interferons and proinflammatory cytokines for antiviral or antitumor effects; inhibitors block sensor activation to prevent pathological inflammation in autoimmune diseases (NIH, 2020; Frontiers in Immunology, 2023).