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Toll-Like Receptors (TLRs) are located on cell surfaces, and Endoplasmic reticulum (ER) membranes, surface of endosomes, lysosomes, endolysosomes of macrophages, dendritic cells, some epithelial cells (e.g., those lining mucous membranes). Their ligands are Lipopolysaccharides (LPS), flagellin, teichoic acid, lipopeptides, ssRNA, dsRNA, CPG DNA
Toll-Like Receptors (TLRs) have a leucine-rich repeat (LRR) ligand-binding domain, that binds MAMPs, DAMPs or PAMPs a single membrane spanning helix, and a cytoplasmic Toll/interleukin-1 receptor (TIR) domain that activates downstream signaling
Che et al. 2019m J. Biomed. Science. 26:90
Microbial associated molecular patterns (MAMPs) bind to Toll-Like Receptors (TLRs) found on both the plasma and endosomal membranes. The binding increases cytokine gene expression through common signal transduction pathways, like the transcription factor NFKB. Interferon beta (IFN-beta) is an antiviral cytokine. TIR domain containing adaptor molecule 1 (TICAM1) and TIR domain containing adaptor protein (TIRAP) are proteins mediating intracellular signaling. In addition to Toll-Like Receptor 4 (TLR-4), CD14 also binds Lipopolysaccharides (LPS)
Given the wide variety of recognized ligands and the intracellular responses mediated by Toll-Like Receptors (TLRs), some accessory molecules are required
Toll-like receptor 3 (TLR-3), Toll-like receptor 7 (TLR-7), and Toll-like receptor 9 (TLR-9) are found both on cell surfaces and intracellularly, allowing for crosstalk with the other Toll-Like Receptors (TLRs)
Toll-like receptors (TLRs) as type I transmembrane glycoproteins are a key family of Pattern Recognition Receptors (PRRs)
Activated Toll-like receptors (TLRs) induce the expression of various pro-inflammatory and antiviral molecules. Toll-like receptors (TLRs) are potential targets for treatment strategies to boost the adaptive immune response to vaccines, control infections , enhance immune responses during tumor treatment, and attenuate immune responses in inflammatory disorders .
Toll-like receptors (TLRs) play a crucial role in the immune system by recognizing Microbial products and initiating immune responses .
Toll-like receptor 1 (TLR-1) , Toll-like receptor 2 (TLR-2) , CD284 (Toll-Like Receptor 4 (TLR-4)), Toll-like receptor 5 (TLR-5) , and Toll-like receptor 6 (TLR-6): These Toll-Like Receptors (TLRs) are primarily expressed on the cell surface and bind to bacterial products. Toll-Like Receptor 3 (TLR-3), Toll-Like Receptor 7 (TLR-7), Toll-like receptor 8 (TLR-8), and Toll-like receptor 9 (TLR-9): These Toll-Like Receptors (TLRs) are located on internal vesicles and bind to bacterial and viral nucleic acids .
Mice express 12 Toll-Like Receptors (TLRs) subtypes (TLR-1-9 and TLR-11-13) but lack a functional orthologue for Toll-like receptor 10 (TLR-10)
Each Toll-like receptor (TLR ) consists of a leucine-rich horseshoe-shaped extracellular domain, a single transmembrane helix, and an Toll-interleukin-1 receptor (TIR) homology domain that interacts with different downstream adaptors to propagate signal transduction
Upon recognizing their ligands, Toll-Like Receptors (TLRs) dimerize. The dimerization enables the recruit of the downstream signaling adaptors, which triggers the activation of specific transcription factors and the subsequent innate immune responses.
They are a member of the pattern recognition receptor (PRR) family and play different roles in recognizing pathogen-associated molecular patterns (PAMPs) expressed by microbial invaders and damage-associated molecular patterns (DAMPs), which are endogenous substances released during tissue damage
Toll-Like Receptors (TLRs) are transmembrane receptors that recognize MAMPs and PAMPs and are constitutively expressed on the surface of intestinal human enteroendocrine cells (TLR2 and -4) and enterocytes (TLR2, -3, -4, -5, and -9), as well as in endosomes (TLR3 and TLR9) (), ready to interact with their extracellular and intracellular ligands, respectively
Up to now, ten members of the Toll-Like Receptors (TLRs) family have been recognized in the human species, compared with at least 13 members in rodents
Toll-Like Receptors (TLRs) promote proliferation of intestinal epithelial cells. Toll-like receptors (TLRs) can also recognize intestinal microorganisms and present them to T lymphocytes
Members of the TLR family recognize bacteria, viruses, fungi and protozoa. In the intricate dance of the immune system, significant interactions take place between Toll-like receptors (TLRs) and certain NOD-like receptors (NLRs) to trigger the production of the pro-inflammatory cytokine interleukin (IL)-1 beta. TLRs are responsible for inducing the production of pro-IL-1 beta and priming NLR-containing multi-protein complexes, known as 'inflammasomes', to react to bacterial products and the remnants of damaged cells. This interaction leads to the activation of caspase-1, which then processes Pro-Interleukin-1 (IL-1) beta (IL-1 beta) into its active form. In this article, we propose that during the initial phase of the host's response to infection, a crucial interplay between these receptor families occurs, offering a significant combinatorial repertoire in the realm of innate immunity.
Toll-Like Receptors (TLRs) are the targets for DAMPs, MAMPs, and PAMPs. These agonists bind to the so-called leucine-rich repeat motifs of the TLRs. Intracellular signaling is triggered via the adapter molecules MYD88, TRIF, TIRAP, and/or TRAM, which leads to the expression and release of pro-inflammatory cytokines and other effector molecules.
Signaling pathways associated with each Toll-like receptors (TLRs) are not identical resulting in different biological responses.
Toll-like receptors (TLRs) may also recognize endogenous ligands induced during inflammation
see also:
CD284 (Toll-Like Receptor 4 (TLR-4)) & Lipopolysaccharides (LPS)
Colitis / Intestinal Inflammation & Interleukin-10 (IL-10)
Colitis / Intestinal Inflammation & Pattern Recognition Receptors (PRRs)
TCRgamma/delta+ IELs
Toll-interleukin-1 receptor (TIR) homology domain