RNA sensing pathways

RNA sensing pathways are essential components of the innate immune system that detect foreign or misplaced ribonucleic acids to initiate protective responses. These pathways primarily utilize two classes of pattern recognition receptors (PRRs): the endosomal Toll-like receptors (TLR3, TLR7, and TLR8) and the cytosolic RIG-I-like receptors (RIG-I and MDA5) (Chow et al., 2018, Nature Reviews Immunology). Upon binding to specific RNA ligands—such as double-stranded RNA or 5-triphosphorylated single-stranded RNA—these receptors trigger signaling cascades through adapter proteins like TRIF or MAVS, leading to the activation of IRF3/7 and NF-κB (Schlee and Hartmann, 2016, Nature Reviews Immunology). This activation results in the robust production of type I interferons and pro-inflammatory cytokines, which establish an antiviral state and bridge innate and adaptive immunity. In clinical development, agonists of these pathways are being investigated as vaccine adjuvants and cancer immunotherapies to stimulate immune surveillance, while antagonists are being explored for autoimmune diseases like systemic lupus erythematosus, where aberrant sensing of self-RNA drives chronic inflammation (Wu and Chen, 2014, Annual Review of Immunology).

Other names

Innate RNA sensingNucleic acid sensing pathwaysTLR/RLR signaling pathwaysViral RNA sensing

Agonism of pattern recognition receptors (TLRs and RLRs) to induce type I interferons and pro-inflammatory cytokines for antiviral or antineoplastic effects; Antagonism of these receptors or inhibition of endosomal acidification to suppress pathological autoimmune signaling.