Host innate immune RNA sensors (RNA-sensing PRRs)

Host innate immune RNA sensors are a specialized class of pattern recognition receptors (PRRs) responsible for detecting non-self or damaged self-RNA molecules within a cell (Chow et al., 2018, Nature Reviews Immunology). These sensors are strategically localized in different cellular compartments: Toll-like receptors (TLR3, TLR7, TLR8) reside in endosomes to monitor extracellular and phagocytosed RNA, while RIG-I-like receptors (RIG-I, MDA5) and other sensors like PKR and OAS1 patrol the cytoplasm (Rehwinkel & Gack, 2020, Nature Reviews Immunology). Upon activation by specific RNA ligands—such as double-stranded RNA or 5-triphosphorylated RNA—these sensors initiate signaling pathways that trigger the production of type I interferons and pro-inflammatory cytokines (Kawai & Akira, 2010, Nature Immunology). This response is critical for establishing an antiviral state and modulating the adaptive immune system. In clinical contexts, dysregulation of these sensors can lead to autoimmune diseases like systemic lupus erythematosus or Aicardi-Goutières syndrome, where the body fails to distinguish self-RNA from viral RNA (Crow, 2014, Nature Reviews Immunology). Consequently, these sensors are major therapeutic targets; agonists are being developed as vaccine adjuvants and cancer immunotherapies to boost immune surveillance, while antagonists are being researched to mitigate chronic inflammatory and autoimmune conditions (Wu & Chen, 2014, Molecular Cell).

Other names

RNA-sensing pattern recognition receptorsCytosolic RNA sensorsEndosomal RNA sensorsRIG-I-like receptorsToll-like receptors (RNA-sensing)Retinoic acid-inducible gene I-like receptors

Agonism of endosomal or cytosolic receptors to induce type I interferon and pro-inflammatory cytokine production for antiviral or antineoplastic effects; antagonism to suppress pathological inflammation in autoimmune conditions.