TIR domain-containing adaptors define the specificity of TLR signaling

The concept that Toll-like receptors (TLRs) recognize specific molecular patterns in various pathogens has been established. In signal transduction via TLRs, MyD88, which harbors a Toll/IL-1 receptor (TIR)-domain and a death domain, has been shown to link between TLRs and MyD88-dependent downstream events leading to proinflammatory cytokine production and splenocyte proliferation. However, recent studies using MyD88-deficient mice have revealed that some TLRs possess a MyD88-independent pathway, which is represented by interferon (IFN)-beta production induced by LPS stimulation. This indicates that additional signaling molecules other than MyD88 exist in the TLR signaling pathway. Indeed, two additional TIR domain-containing adaptors, TIRAP/Mal and TRIF, have recently been identified. Both define the specific biological responses of each TLR.