Innate immune RNA-sensing pathways (RNA-sensing pathways)

Innate immune RNA-sensing pathways are critical components of the host defense system designed to detect foreign or mislocalized RNA molecules, primarily from viruses or damaged host cells. These pathways utilize various pattern recognition receptors (PRRs), including the cytosolic RIG-I-like receptors (RIG-I and MDA5) and endosomal Toll-like receptors (TLR3, TLR7, and TLR8), to recognize specific RNA motifs such as double-stranded RNA or single-stranded RNA with 5-triphosphate ends (Schlee & Hartmann, 2016; Nat Rev Immunol). Upon activation, these sensors trigger signaling cascades involving adapter proteins like MAVS, TRIF, or MyD88, ultimately leading to the production of Type I interferons and pro-inflammatory cytokines (Kawai & Akira, 2010; Nat Immunol). Dysregulation of these pathways is linked to various pathologies; overactivation can lead to autoimmune disorders like systemic lupus erythematosus or Aicardi-Goutières syndrome, while insufficient activation can result in increased susceptibility to viral infections (Roers et al., 2016; Immunity). In oncology, agonists of these pathways are being developed as vaccine adjuvants and cancer immunotherapies to stimulate the tumor microenvironment and enhance anti-tumor T-cell responses (Kanzler et al., 2007; Nat Med). Conversely, small molecule antagonists targeting TLR7/8 are currently in clinical trials for the treatment of systemic lupus erythematosus to reduce the chronic interferon signature (Vasilakos & Tomai, 2013; Expert Rev Vaccines). The therapeutic challenge lies in achieving localized activation to avoid systemic cytokine-related toxicities while maintaining sufficient potency for clinical efficacy (Wu & Chen, 2014; Annu Rev Immunol).

Other names

Nucleic acid sensing pathwaysRNA pattern recognition receptor pathwaysRLR signaling pathwayEndosomal TLR signaling pathwayViral RNA sensing

Agonism or antagonism of pattern recognition receptors (PRRs) to modulate the production of Type I interferons and pro-inflammatory cytokines via MAVS, TRIF, or MyD88 adapter proteins.