TLR3 is a member of the toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLR3 recognizes double-stranded RNA, a form of genetic information carried by some viruses such as reoviruses.

Where is TLR3 expressed?

TLR3 is expressed in various tissues and cells. In the human central nervous system, TLR3 is expressed constitutively in neurons, astrocytes, and microglia, suggesting a role in the response to viruses causing encephalopathy. In immune cells, only myeloid DCs and macrophages express TLR3.

Which TLRs are in endosomes?

The endosomal Toll-like receptors (TLR3, TLR7 and TLR9) have been implicated in the pathogenesis of autoimmune diseases. Their signaling pathways show remarkable similarities and yet the outcomes following activation of each of these TLRs lead to clinically distinct autoimmune disease phenotypes.

What is the ligand of TLR3?

Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a PAMP associated with viral infections. The ligand of choice for TLR3 is a synthetic analog of dsRNA known as polyinosinic-polycytidylic acid (poly(I:C) or poly(rI):poly(rC)).

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Different types of TLRs TLR1 and TLR2 are awarded to teachers undertaking sustained additional responsibility. TLR3 payments are awarded for teachers who are taking on a time-limited school improvement project or one-off responsibility.

What does TLR3 bind to?

dsRNA
Analysis of the crystal structure of a complex comprising TLR3 and dsRNA revealed that TLR3 binds to dsRNA molecules at two sites located at opposite ends of the TLR3 horseshoe [20,21]. Furthermore, data also suggest that TLR3 primarily senses unmethylated RNA molecules [22].

How does TLR work?

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses.

Why do some TLRs exist in the endosome?

Most endosomal TLRs recognize microbial derived nucleic acids. The ectodomains of these nucleic acid sensing TLRs undergo proteolytic processing in endosomes to generate functional receptors capable of signaling upon ligand recognition.

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How is TLR3 activated?

The NF-κB branch of TLR3 is activated by TRIF-dependent recruitment of RIP1, TAK1, and IKK. Activation of these transcription factors leads to their nuclear translocation, where they bind to their respective promoter elements of the target genes.

Where is TLR3 expressed in endosomes?

TLR3 is localized to cell surfaces and endosomes in fibroblasts, macrophages, and some epithelial cell lines. 18 In contrast, myeloid DCs only express TLR3 intracellularly. 34 Immunofluoresence analysis has shown that endogenous TLR3 is localized to the early endosome, but not to late endosomes/lysosomes.

What is TLR 3 and where is it found?

TLR-3 is found on plasma membranes, where it is believed to contact dsRNA after the lysis of infected cells and release of dsRNA into the extracellular milieu. Of note, additional evidence suggests that TLR-3 is found inside cells in vesicles associated with the endocytic pathway.

How does TLR3 recognize dsRNA?

TLR3 preferentially recognizes dsRNA derived from the viral genome presented extracellularly, i.e., the viral genome released from damaged host cells and/or viral particles [18,19]. The dsRNA molecules must be at least 40–50 bp in length to induce TLR3 signaling [14,19].

What RNA molecules activate TLR3 in viral infection?

TLR3 recognizes viral dsRNA and poly (I:C), but it is still unknown what RNA molecules activate TLR3 in viral infection and sterile inflammatory states.