TRIF is a member of the Toll/interleukin-1 receptor (TIR) family, a group of proteins that include the Toll-like receptors (TLRs). TLRs are signaling molecules that recognize different pathogen-associated molecular patterns (PAMPs) and serve as an important link between the innate and adaptive immune responses. TRIF, along with other molecules such as TIRP, TIRAP, and MyD88, serves as an adaptor protein to several of the TLR molecules. Following activation of TLR3 and TLR4, TRIF engages the kinase TBK1 and allows its subsequent activation of the interferon regulatory factor (IRF)-3. TRIF is also involved in the activation of TNF receptor associated factor (TRAF)-6, and ultimately the activation of NF-kappaB.

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