Toll-like Receptors and their Function
- Toll-like receptors (TLRs) are immune receptors expressed on various immune cells and non-immune cells.
- TLRs recognize molecules shared by pathogens and initiate immune responses.
- TLR activation leads to signal transduction and the activation of downstream proteins.
- Bacterial factors may be phagocytosed and digested, while viral factors may induce cell death.
- TLRs play a role in the link between innate and adaptive immunity.

Toll-like Receptor Superfamily
- TLRs are a type of pattern recognition receptor (PRR).
- TLRs recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
- TLRs belong to the interleukin-1 receptor/toll-like receptor superfamily.
- TLRs have Toll-interleukin receptor (TIR) domains.
- TLRs can be classified into three subgroups based on their TIR domains.

Toll-like Receptors in Different Organisms
- TLRs are present in vertebrates, invertebrates, bacteria, and plants.
- TLRs are conserved components of the immune system.
- TLRs have been identified in the mammalian nervous system.
- Different mammalian species have varying numbers of TLRs.
- Some TLRs found in humans are not present in all mammals, and vice versa.
- Toll signalling is involved in the immune response of fruit flies.
- Fruit flies have innate immune responses and lack adaptive immunity.
- The toll pathway in fruit flies is similar to mammalian TLR signalling.
- The toll pathway is activated by different stimuli, such as bacteria and fungi.
- Drosophila have multiple toll family and spz family genes involved in immune response.

Toll-like Receptors and their Characteristics
- TLR2 is also known as CD282.
- TLR2 is a toll-like receptor.
- TLR2 recognizes specific molecules and initiates immune responses.
- TLR2 plays a role in host defense against pathogens.
- TLR2 has been extensively studied in the context of immune responses.
- Human cells do not express TLR11, but mice cells do.
- Mouse-specific TLR11 recognizes uropathogenic E.coli and Toxoplasma gondii.
- TLR11 recognizes flagellin from Salmonella.
- Normal mice do not get infected by oral Salmonella Typhi due to TLR11 recognition.
- TLR11 deficient knockout mice are efficiently infected and can act as a disease model of human typhoid fever.

Toll-like Receptors and their Medical Relevance
- Toll-like receptors recognize molecules associated with threats.
- Pathogen-associated molecules are difficult to change through mutation and are evolutionarily conserved.
- TLR ligands are present in most pathogens and may be present in pathogen-derived vaccines.
- Commercially available vaccines have been assessed for their TLR ligand capacity to activate immune cells.
- Ligands recognized by TLRs include lipopolysaccharides, flagellin, viral RNA, and CpG islands in DNA.
- Toll-like receptors can also bind to host molecules.
- Endogenous ligands include fibrinogen, heat shock proteins, HMGB1, extracellular matrix components, and self DNA.
- Endogenous ligands are produced as a result of non-physiological cell death.
- Under inflammatory and autoimmune conditions, self DNA can form a complex with endogenous proteins and gain access to endosomal TLRs.
- Endogenous ligands may participate in autoimmune diseases.
- TLRs function as dimers, with some forming heterodimers.
- Co-receptors may be required for full ligand sensitivity, such as MD-2 for TLR4's recognition of LPS.
- Endosomal TLRs recognize nucleic acids and activate inflammatory cytokines and type I interferons.
- Adapter proteins and kinases mediate TLR signaling.
- MyD88-dependent and TRIF-dependent pathways are the two distinct signaling pathways of TLRs.
- Imiquimod and resiquimod are TLR7 agonists used in dermatology and cancer immunotherapy.
- TLR ligands are being tested as vaccine adjuvants.
- TLR4 is important for the long-term side effects of opioids.
- TLR4 activation leads to the release of inflammatory modulators and is involved in opioid tolerance.
- Morphine-induced TLR4 activation attenuates pain suppression by opioids and enhances the development of opioid tolerance.

Toll-like receptor (Wikipedia)

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles (because they are sensors of nucleic acids).

Toll-like receptor
The curved leucine-rich repeat region of toll-like receptors, represented here by TLR3
Identifiers
Symbol	Toll-like receptor
Membranome	7
PIRSF037595

TLRs received their name from their similarity to the protein coded by the toll gene.