Pattern recognition receptors for double-stranded RNA (dsRNA PRRs) (dsRNA PRRs)

Pattern recognition receptors for double-stranded RNA (dsRNA PRRs) represent a functional class of innate immune sensors that detect double-stranded RNA, a hallmark of viral replication and cellular damage (Kawai & Akira, 2010, Nature Immunology). This group includes endosomal receptors like Toll-like receptor 3 (TLR3) and cytoplasmic sensors such as Retinoic acid-inducible gene I (RIG-I) and Melanoma differentiation-associated protein 5 (MDA5) (UniProt). Upon activation, these receptors initiate signaling pathways through adapter proteins like TRIF or MAVS, leading to the production of Type I interferons and pro-inflammatory cytokines (PubMed: 20404850). These molecules play a critical role in defending against viral infections and are increasingly targeted in cancer immunotherapy to turn cold tumors hot by stimulating the tumor microenvironment. Synthetic dsRNA analogues, such as Poly(I:C) and Rintatolimod, act as agonists for these receptors and are used as vaccine adjuvants or direct anti-tumor agents (NIH/NCI). However, because this target definition encompasses multiple distinct proteins with different localizations and signaling outcomes, it is considered a broad classification rather than a single therapeutic target. Therapeutic challenges include the risk of systemic cytokine storms and the potential for inducing autoimmune reactions due to chronic interferon signaling (StatPearls).

Other names

Double-stranded RNA sensorsRNA-sensing pattern recognition receptorsdsRNA sensorsCytoplasmic and endosomal dsRNA receptors

Agonism of innate immune sensors to induce Type I interferon and pro-inflammatory cytokine production.