TLR-induced signalling pathways. When activated, toll-like receptors (TLRs) either heterodimerize, such as TLR2 with either TLR1 or TLR6, or homodimerize to induce signalling pathway activation. Signalling is regulated by adaptor molecules. MyD88 is an adaptor used by all TLRs aside from TLR3. TLR7 recruits MyD88 directly, whereas TLR4 and TLR2 recruit MyD88 through bridging adapter TIRAP. MyD88 recruitment ultimately leads to the activation of nuclear transcription factor NFκB by releasing the p50 and p65 subunits from the NFκB inhibitor IκB. Activated NFκB then translocates to the nucleus to induce the expression of inflammatory cytokines. When activated by TLR7, MyD88 can also induce the phosphorylation and dimerization of interferon regulatory factor 7 (IRF7). This activation of IRF7 triggers the induction of IFNα. An alternative signalling pathway downstream of TLR4 involves the recruitment of adaptor molecule TRIF through bridging protein TRAM. This ultimately leads to activation of IRF3 and subsequent IFNβ induction (For review see ). Note that for simplicity the full complement of extracellular proteins involved in TLR for function are not represented in this diagram. Specifically, TLR4 requires MD-2, CD14 and LPS binding protein to bind LPS efficiently.