Innate Adaptations

Viruses, bacteria, and fungi express broadly distinct molecular patterns that activate innate arms of the immune system. Most prominently, the Toll-like receptors (TLRs) use these pathogen-specific cues to elicit intracellular signals that can be either dependent or independent of the Toll/interleukin 1 receptor (TIR) domain-containing adaptor proteins, MyD88 and TIRAP. Yamamoto et al. define a third TIR adaptor, TRIF, as critical for MyD88-independent signaling by particular TLRs. Cells deficient in TRIF failed to initiate either the interferon regulatory factor-3 or nuclear factor κB pathways in response to TLR3 or TLR4 activation, but responded normally to activation of other TLR family members. M. Yamamoto, S. Sato, H. Hemmi, K. Hoshino, T. Kaisho, H. Sanjo, O. Takeuchi, M. Sugiyama, M. Okabe, K. Takeda, S. Akira, Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 301, 640-643 (2003). [Abstract] [Full Text]