TLR2
Description
The TLR2 (toll like receptor 2) is a protein-coding gene located on chromosome 4.
Toll-like receptor 2, also known as TLR2 or CD282, is a protein encoded by the TLR2 gene in humans. It is a member of the toll-like receptor (TLR) family, which plays a crucial role in recognizing pathogens and activating the innate immune system. TLRs are highly conserved across species and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) expressed on infectious agents and trigger the production of cytokines essential for developing effective immunity. TLR2 is primarily expressed in peripheral blood leukocytes and mediates the host response to Gram-positive bacteria and yeast by stimulating NF-κB. In the intestine, TLR2 regulates the expression of CYP1A1, a key enzyme in detoxifying carcinogenic polycyclic aromatic hydrocarbons like benzo(a)pyrene. The immune system identifies and eliminates foreign pathogens.
TLR2 cooperates with LY96 to initiate the innate immune response against bacterial lipoproteins and other microbial cell wall components. It also works with TLR1 or TLR6 to trigger the innate immune response against bacterial lipoproteins or lipopeptides. TLR2 activates NF-kappa-B, leading to cytokine secretion and the inflammatory response through MYD88 and TRAF6. It can also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. TLR2 recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM), and B.burgdorferi outer surface protein A lipoprotein (OspA-L) in collaboration with TLR6. Stimulating monocytes in vitro with M.tuberculosis PstS1 primarily activates p38 MAPK and ERK1/2 through TLR2, but also partially through TLR4. TLR2 also mediates MAPK activation in response to bacterial peptidoglycan. TLR2 acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH, and PstS1. Some lipoproteins require additional coreceptors (TLR1, CD14, and/or CD36). These lipoproteins act as agonists to modulate antigen-presenting cell functions in response to the pathogen. M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) stimulates NF-kappa-B expression through TLR2. TLR2 recognizes M.tuberculosis major T-antigen EsxA (ESAT-6), which inhibits downstream MYD88-dependent signaling (observed in mice). TLR2 forms activation clusters consisting of various receptors depending on the ligand. These clusters initiate signaling from the cell surface and are then transported to the Golgi via a lipid-raft dependent pathway. In response to diacylated lipopeptides, TLR2 forms the cluster TLR2:TLR6:CD14:CD36, while in response to triacylated lipopeptides, it forms TLR2:TLR1:CD14. TLR2 is essential for normal M.tuberculosis uptake, a process inhibited by M.tuberculosis LppM. TLR2 interacts with LY96, TLR1, and TLR6 through its extracellular domain. TLR2 appears to exist as heterodimers with either TLR1 or TLR6 before ligand stimulation. Upon encountering their corresponding ligands, these heterodimers assemble into larger oligomers, forming further heterotypic associations with other receptors such as CD14 and/or CD36. TLR2 binds MYD88 through its TIR domain. It interacts with TICAM1, CNPY3, ATG16L1, PPP1R11, TICAM2, and TIRAP. TLR2 interacts with M.tuberculosis EsxA, M.bovis MPB83, and Staphylococcus aureus protein SSL5.
TLR2 is also known as CD282, TIL4.
