What is the role of TLR3?
What is the role of TLR3?
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.
What activates TLR3?
TLR3 activation by dsRNA leads to direct induction of antiviral genes in virus-infected cells. Although TLR3 signaling is activated by a variety of virus infection, the role of TLR3 in viral pathogenesis is complex, with both pro- and anti-viral effects.
Where is TLR3 located in the cell?
TLR3 is localized to cell surfaces and endosomes in fibroblasts, macrophages, and some epithelial cell lines. In contrast, myeloid DCs only express TLR3 intracellularly. Immunofluoresence analysis has shown that endogenous TLR3 is localized to the early endosome, but not to late endosomes/lysosomes.
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 cytokines are produced by TLR3 activation?
TLR3 is expressed by various immune or non-immune cells, including dendritic cells (DCs),3 macrophages,4 natural killer (NK) cells,5,6 fibroblasts7 and epithelial cells. Sensing of viral dsRNA by TLR3 leads to the secretion of type I interferon (IFN) and other pro-inflammatory cytokines.
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)).
What Cytokines are produced by TLR3 activation?
What is TLR3 ligand?
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.
How do Toll-like receptors work?
Toll-like receptors (TLRs) recognize microbes by binding to pathogen-associated molecular patterns. Scientists theorized that Toll-like receptors (TLRs) would initiate immune responses to pathogens because of their amino acid sequence similarities to Toll.
Is TLR3 intracellular?
Although TLR3, 7 and 9 all reside in intracellular compartments, the mechanisms that dictate their location are different for each. The intracellular location of TLR3 is determined by a 23- amino acid sequence present in the linker region between transmembrane and TIR domain (20).
What happens when endosomal TLR3 is activated?
Endosomal TLR3 is regarded as a sentinel to RNA viruses, and activation of TLR3 leads to TRIF (TIR domain-containing adaptor-inducing IFN-β)-dependent IFN production and nuclear factor-κB (NF-κB)-dependent proinflammatory cytokine production 3.
How does the TLR mediate the immune response?
TLR mediate the antiviral immune responses by recognizing virus infection, activating signaling pathways and inducing the production of antiviral cytokines and chemokines. ssRNA and dsRNA viruses can be recognized by TLR7/8 and TLR3, respectively.
Where are the TLR receptors located in the cell?
The TLR family includes receptors residing both at the cell surface and intracellularly, highlighting the specialization of receptor subsets for particular tasks. Many of the unique properties of the intracellular receptors have only recently been deciphered.
Why is clec18a a TLR3 co receptor?
Thus, CLEC18A is a TLR3 co-receptor, and may contribute to the differential immune responses to poly (I:C) and IAV infection between human and mouse.
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