Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific of microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.

Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons.

Defects in TLR3 are associated with herpes simplex encephalitis type 2 (HSE2) [MIM:613002]. HSE is a rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. Note=TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.

Belongs to the Toll-like receptor family.
Contains 22 LRR (leucine-rich) repeats.
Contains 1 LRRCT domain.
Contains 1 LRRNT domain.
Contains 1 TIR domain.

ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.

Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.

Endoplasmic reticulum membrane. Endosome membrane.