Toll-like Receptor Signaling Pathway

Toll-like receptors (TLR) are membrane-bound receptors identified as Toll homologues in Drosophila melanogaster. They belong to the pathogenic pattern recognition receptors of innate immunity. They can recognize proteins, nucleic acids and lipids of invading pathogenic microorganisms, as well as their intermediates and metabolites synthesized during the reaction. For example, lipopolysaccharides of gram-negative bacteria, peptidopolysaccharides of Gram-positive bacteria and double-stranded RNA of viruses are pathogen-associated molecular patterns with highly conserved molecular structures. The subcellular localization of TLR family members are different, including TLR1, TLR2, TLR4, TLR5, TLR6 and TLR11 distributed on the cell surface, and TLR3, TLR7, TLR8 and TLR9 located in endosomes/lysosomes. Recognition of pathogens by TLRs stimulates rapid activation of innate immunity by inducing the production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling can be divided into two categories. One is the myd88-dependent pathway, which leads to the production of proinflammatory cytokines and rapid activation of NF-κB and MAPK. The other category is the myd88-independent pathway, associated with the induction of interferon-β and interferon-inducible genes, maturation of dendritic cells and slow activation of NF-κB and MAPK. TLRS are the first line of defense against pathogen invasion and play a key role in inflammation, immune cell regulation, survival, and proliferation