Disease:Defects in TLR3 are the cause of TLR3-deficient herpes simplex encephalitis (HSE) [MIM:603029]. 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. ,Disease:Genetic variation in TLR3 is associated with susceptibility to progression to geographic atrophy in age-related macular degeneration [MIM:612479]. Age-related macular degeneration (ARMD) is the most common cause of irreversible vision loss in the developed world. In most patients , the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch's membrane. ARMD is likely to be a mechanistically heterogeneous group of disorders , and the specific disease mechanisms that underlie the vast majority of cases are currently unknown. However , a number of studies have suggested that both genetic and environmental factors are likely to play a role. Geographic atrophy (extensive atrophy of the retinal pigment epithelium and overlying photoreceptors) is an advanced form of 'dry' (nonneovascular or nonexudative) ARMD. ,Function:Participates in the innate immune response to microbial agents. Mediates the innate immune response to ds-RNA , a sign of viral infection. Acts via MYD88 and TRAF6 , leading to NF-kappa-B activation , cytokine secretion and the inflammatory response. ,online information:TLR3 mutation db ,PTM:Heavily N-glycosylated , except on that part of the surface of the ectodomain that is involved in ligand binding. ,similarity:Belongs to the Toll-like receptor family. ,similarity:Contains 1 TIR domain. ,similarity:Contains 22 LRR (leucine-rich) repeats. ,subunit:Binds MYD88 via their respective TIR domains (By similarity) . Interacts with TICAM1. Homodimer formation is triggered by ligand binding and is required for TLR3 signaling. Binding of ds-RNA is required for the interaction with SRC. ,tissue specificity: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. ,
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