TLR3

TLR3 (Toll-like receptor 3) is a pattern-recognition receptor of the innate immune system that detects viral double-stranded RNA (dsRNA), a conserved molecular signature generated during many viral infections^[1][2]. TLR3 engagement by dsRNA initiates signaling that activates NF-κB, induces type I interferons, and promotes inflammatory cytokine production, thereby establishing antiviral innate immune responses^[1][3]. Mechanistically, TLR3 recognizes dsRNA through its extracellular leucine-rich repeat domain and forms ligand-induced dimers and higher-order multimeric complexes along dsRNA, which enhance signal transduction efficiency^[2][4]. TLR3 predominantly senses extracellular or endosomal dsRNA derived from virus-infected cells, damaged tissues, or synthetic dsRNA analogs, linking pathogen recognition to host defense programs^[5][6]. In disease and experimental models, TLR3 signaling contributes to antiviral immunity and serves as a widely used pathway for investigating innate immune activation and interferon-mediated responses^[1][5]. Compared with related nucleic acid-sensing Toll-like receptors such as TLR7 and TLR8, which primarily recognize single-stranded RNA, TLR3 is distinguished by its selective recognition of dsRNA and its specialized role in antiviral sensing^[3][7]. For experimental applications, the synthetic dsRNA analog poly(I:C) is a well-established TLR3 agonist that induces interferon production, inflammatory cytokines, and dendritic cell maturation, making it a valuable tool for mechanistic studies of innate immunity and immune modulation^[1][8].