Toll-like Receptor

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen. TLRs can recognize bacteria, viruses, fungi, protozoa, and endogenous ligands, such as heat shock proteins and fibrinogen. TLRs are expressed in innate immune cells such as dendritic cells (DCs) and macrophages as well as non-immune cells such as fibroblast cells and epithelial cells. They are located either within the cell membrane (TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10) or in the endosome (TLR3, TLR7, TLR8, TLR9, TLR11, TLR12, and TLR13). Up to now, 10 TLR (TLR1-TLR10) have been identified in human and 12 (TLR1-TLR9, TLR11-TLR13) in mouse. The typical TLRs are type 1 transmembrane glycoprotein receptors that consist of three structural domains: 1) Extra-cellular or N-terminal domain composed of tandem repeats of a motif called leucine-rich repeat (LRR) responsible for ligand recognition; 2) A cytoplasmic Toll/IL-1 receptor (TIR) domain contributing to signaling cascade upon TLR activation; 3) The transmembrane region involving in TLR dimerization and stabilization. TLRs can be categorized as the IL-1 receptor/TLR superfamily by their structural similarity. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses.