Toll-like receptors (TLR) make the first contact with invading bacteria and function as sensors of infection for immune cells. But the signalling pathway is apparently identical for all TLRs and it is not clear how different toll receptors can induce distinct immune responses. In September Nature Immunology, Tiffany Horng and colleagues from Yale University School of Medicine describe a new cytoplasmic adapter protein for TLR4, called TIRAP, that helps explain the molecular signaling behind microbial recognition.

Horng et al. identified TIRAP (TIR domain–containing adapter protein) because of its domain similarities with TLR4. Working on mice deficient in MyD88 (an essential protein in the classical Toll signaling pathway) they showed that TIRAP is part of an alternative signaling route for immune responses induced by Toll-like receptor 4, but not Toll-like receptor 9 (Nat Immunol 2001, 2:835-841).

Interfering with the TIRAP-TLR4 interaction may inhibit responses to bacterial components such...

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