Innate RNA pattern-recognition receptors (PRRs) (PRRs)

Innate RNA pattern-recognition receptors (PRRs) are a specialized group of immune sensors that detect foreign or mislocalized RNA to initiate defensive responses. This group includes endosomal Toll-like receptors (TLR3, TLR7, and TLR8) and cytosolic RIG-I-like receptors (RIG-I and MDA5). TLR3 recognizes double-stranded RNA, while TLR7 and TLR8 detect single-stranded RNA, primarily in immune cells like dendritic cells and macrophages. In the cytoplasm, RIG-I and MDA5 function as RNA helicases that identify viral replication intermediates, signaling through the MAVS protein to induce type I interferons and pro-inflammatory cytokines. These sensors are critical for the host response to viral infections such as influenza and COVID-19, but their chronic activation is implicated in autoimmune disorders like systemic lupus erythematosus. In cancer therapy, agonists of these receptors, such as imiquimod and poly(I:C), are used to stimulate the tumor microenvironment and promote anti-tumor immunity. Therapeutic strategies also include the development of antagonists to treat interferonopathies caused by the sensing of self-RNA. Overall, these receptors represent a vital link between innate detection and the orchestration of adaptive immunity.

Other names

Toll-like receptor 3Toll-like receptor 7Toll-like receptor 8Retinoic acid-inducible gene IMelanoma differentiation-associated protein 5TLR3TLR7TLR8RIG-IMDA5RIG-I-like receptorsRLRsDDX58IFIH1Endosomal RNA sensorsCytosolic RNA sensors

Agonism of endosomal (TLR3, TLR7, TLR8) and cytosolic (RIG-I, MDA5) receptors to trigger the production of type I interferons and pro-inflammatory cytokines, thereby enhancing antiviral and anti-tumor immune responses; or antagonism to inhibit pathological immune activation in autoimmune and inflammatory diseases.