Toll-like receptors (TLRs) represent a family of proteins that are involved in the innate sensing of conserved microbial components. They are composed of an extracellular domain containing leucine-rich repeats and a cytoplasmic Toll/interleukin-1 receptor/resistance (TIR) domain that is responsible for mediating downstream signaling cascades and subsequent inflammatory response, ultimately leading to the eradication of infectious agents.
Toll-like receptors were originally described as proteins with homology to the protein Toll, which was first identified in Drosophila melanogaster. In flies, Toll served a regulatory function in the embryonic dorsoventral polarity and was later shown to be an essential component of the Drosophilainnate immune system. Based on the fact that Toll serves an immune function in Drosophila, it was proposed that TLRs might “activate adaptive immunity” in mammals, but the precise function of TLRs was revealed by forward genetics.