Schematic representation of Toll-like receptor (TLR) signaling pathways. All TLRs except for TLR3 are thought to share the MyD88-dependent pathway that activates NF-κB and mitogen-activated protein (MAP) kinases, leading to the induction of inflammatory cytokine genes. Interleukin-1 receptor-associated kinases (IRAKs) and TRAF6 are located downstream of MyD88. TIRAP is involved in the MyD88-dependent pathway downstream of TLR2 and TLR4. TRIF is utilized in the TLR3-mediated and TLR4-mediated activation of interferon regulatory factor (IRF)3 and the subsequent induction of IRF3-dependent gene expression such as interferon-β (IFN-β). TRAM is specifically involved in the activation of IRF3 in TLR4 signaling. The complex of TBK1/IκB kinase-i (IKK-i) is responsible for the activation of IRF3 downstream of TRIF in TLR3 and TLR4 signaling. TRAF6 is also involved in the TRIF-dependent activation of NF-κB and MAP kinases. Receptor-interacting protein (RIP) mediates TRIF-dependent NF-κB activation. DD, death domain.