Toll-Like Receptors in Secondary Obstructive Cholangiopathy

Table 1

Toll-like receptor(TRLs) characteristics. Some TLRs recognize proteins, lipids, and nucleic acids from RNA or DNA of pathogens by inducing innate immune response. Stimulation of TLRs starts with the activation of intracellular signals resulting in secretion of proinflammatory cytokines such as type 1 IFN, TNF-α, and IL-6 depending on the causal agent.

	Location	Function	Stimulates	Inhibits or interferes
Toll-like receptor (TLR)	(i) Transmembrane receptors expressed in most immune cells including polymorphonuclear and epithelial cells; (ii) Intracellular receptor function	(i) Induction of phagocytosis, opsonization, and production of inflammatory mediators,	(i) Innate and adaptive inflammatory response	(i) The spread of the pathogen
TLR-1	(i) Expressed on the surface of all cells at high levels; (ii) Recognizes peptidoglycan; (iii) Found on macrophages and neutrophils	(i) Recognition of PAMP from Gram-positive bacteria; (ii) Reduction of cytokines production	(i) Heterodimers increasing the specificity of their ligands	(i) Phenol-soluble modulin
TLR-2	(i) Expressed on cell membranes surface; (ii) Found on macrophages and neutrophils	(i) Lipid transport through lipoproteins uptake; (ii) Formation of heterodimers; (iii) Recognition of triacylated lipopeptides, structures of peptidoglycan, lipoteichoic acid and lipoproteins of Gram-positive bacteria, spirochetal LPS, zymosan from fungi, Treponema maltophilum glycopeptides, glucoinositol phospholipid from Trypanosoma cruzi and modulin	(i) Requires the presence of leucine-rich cofactors such as CD14	(i) Deficiency protects from nonalcoholic fatty liver disease
TLR-3	(i) Intracellular expression on endosomes of myeloid DCs	(i) Reaction to dsRNA from viruses and apoptotic and/or necrotic cells	(i) Type I IFN production during viral infections and NF-κB	(i) Antagonist
TLR-4	(i) Expressed on all cell surface	(i) First to respond to LPS ligand; (ii) Detection of LPS in Gram-negative bacteria membrane	(i) IRAK-M; (ii) Cellular components; (iii) Endogenous ligands which are released or increased during tissue injury and matrix degradation; (iv) Synthesis of inflammatory cytokines and type I IFN	(i) IRAK-1, MyD88, and NF-κB
TLR-5	(i) Expressed on all cell surface	(i) Recognition of bacterial flagellin protein of Salmonella typhimurium; (ii) Induction of inflammatory responses via a MyD88-dependent or independent pathway	(i) Initiation or amplification of Th2-type; (ii) Innate immunity; (iii) Apoptotic signaling pathways and proinflammatory	(i) I-κB degradation; (ii) NF-κB activation for soared tissue
TLR-6	(i) Expressed in myeloid and monocyte-derived dendritic cells (DCs); (ii) Not expressed on plasmacytoid DCs (pDCs)	(i) Recognition of Mycoplasma and Borrelia Burgdorferi; (ii) Differences between acylated lipopeptides of pathogen microorganisms; (iii) Formation of heterodimers with TLR-1, TLR-2, and TLR-10	(i) Specificity of ligands from TLR-1, TLR-2, and TLR-10	(i) Antagonist
TLR-7	(i) Expressed on endosome of dendritic cells, human plasmacytoid cells, myeloid cells, and monocyte-derived cells	(i) Recognition of imidazoquinolines	(i) Type I IFN production during viral infections; (ii) Agonists of TLR-7	(i) Antagonists
TLR-8	(i) Intracellular expression	(i) Detection of pathogen-derived nucleic acids (ssRNA)	(i) Type I IFN MyD88-dependent	(i) Antagonists
TLR-9	(i) Intracellular expression	(i) Recognition of bacterial DNA with unmethylated motifs; (ii) Activation in viral infections; (iii) Recognition of DNA from viral infections	(i) Type I IFN	(i) Antagonists
TLR-10	(i) TLR2/1, TLR2/10 complexes recruit the proximal adaptor MyD88	(i) Receptor complex requires TLR-2 for innate immune recognition; (ii) Related to TLR1 and TLR6; (iii) Mediate immune responses to a variety of microbe and fungi	(i) Proximal adaptor MyD88 to the activated receptor complex; (ii) Without a defined agonist alone or in cooperation with TLR2	(i) TLR-induced signaling, including NF-κB-, IL-8, or IFN-beta-driven reporters