Signaling pathway of toll-like receptors (TLRs). After recognition of the ligand by the extracellular domain of TLRs, adaptor proteins are recruited to the TIR domain and initiate intracellular signaling. Four types of adaptor proteins have been identified in mammals: MyD88, TRIF, TRAM, and TIRAP. The recruitment of IRAK and TRAF6 to the adaptor proteins leads to nuclear translocation of NF-kB. TRAF6 can also activate MAPK kinases (MKK) leading to the activation of transcription factor AP-1. This pathway is common to all the TLRs, except for TLR3 which uses TANK-binding kinase 1 (TBK1) and results in the activation of IRF3.