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.

What is TLR3?

TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response.

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 are the intracellular TLR used to detect?

Intracellular TLRs recognize nucleic acids derived from bacteria and viruses, and also recognize self-nucleic acids in disease conditions such as autoimmunity (9). TLR3 recognizes viral double-stranded RNA (dsRNA), small interfering RNAs, and self-RNAs derived from damaged cells (10–12).

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.

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.

Is TLR3 intracellular or extracellular?

TLR3, TLR7, TLR8, TLR9, and probably TLR13 of mice are expressed intracellularly within the endoplasmic reticulum (ER), endosomes, multivesicular bodies, and lysosomes.

How are TLRs activated?

The toll pathway is activated by different stimuli, such as Gram positive bacteria, fungi and virulence factors. First, the Spätzle processing enzyme (SPE) is activated in response to infection and cleaves spätzle (spz). Cleaved spätzle then binds to the toll receptor and crosslinks its ectodomains.

What does TLR1 recognize?

TLR1 recognizes pathogen-associated molecular pattern with a specificity for gram-positive bacteria. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity.

What cells express TLR3?

TLR3 Expression in SLE In humans TLR3 is restricted to myeloid dendritic cells, but in mice TLR3 is also expressed on macrophages [25, 29]. TLR3 has been shown to be expressed in the kidney and on glomerular mesangial cells [17, 30, 31].