Toll-like receptors

Toll-like receptors show homology with the Drosophila Toll protein and the human interleukin-1 receptor family, and are transmembrane proteins that recognize extracellular or endosomal pathogen-associated molecular patterns. The specificity of Toll-like receptor signaling is due to adaptor proteins containing Toll–interleukin 1 receptor (TIR) domains. Five TIR adaptors display activating functions: MyD88, Mal, TRIF, TRAM, and SARM.

The TLR family is characterized by the presence of leucine-rich repeats (which mediates ligand binding) and a Toll/interleukin-1 receptor-like domain (which mediates interaction with intracellular signaling proteins). Most identified TLR ligands are either conserved microbial products that signal the presence of an infection, or endogenous ligands that might signal other danger conditions. TLRs trigger signals evoking synthesis and secretion of cytokines and activation of host defenses through NF-κB, MAP kinases, and costimulatory molecules.

receptor	ligand	adaptor proteins
TLR1	triacyl lipoproteins	MyD88/MAL
TLR2	lipoproteins; G+ peptidoglycan; lipoteichoic acids; fungi; viral glycoproteins	MyD88/MAL
TLR3	double-stranded RNA (viruses), poly I:C	TRIF
TLR4	lipopolysaccharide (LPS); viral glycoproteins	MyD88/MAL/TRIF/TRAM
TLR5	flagellin	MyD88
TLR6	diacyl lipoproteins	MyD88/MAL
TLR7	small synthetic compounds; single-stranded RNA	MyD88
TLR8	small synthetic compounds; single-stranded RNA	MyD88
TLR9	unmethylated CpG DNA	MyD88
TLR10	unknown	unknown
TLR11	profilin	MyD88
TLR12	unknown	unknown
TLR13	unknown	unknown