Catching the adaptor-WDFY1, a new player in the TLR-TRIF pathway.

The innate immune system detects microbes and abnormal self through pattern recognition receptors (PRRs), which detect molecules that are either specific for microbes (such as lipopolysaccharide), present in much higher concentrations during infection (such as double-stranded RNA), or present in aberrant locations (such as cytosolic DNA) [1]. The Toll-like receptors (TLRs) are the best-described set of PRRs. TLRs are membrane-bound receptors localized on the plasma membrane and in endosomes, the ligand-binding regions of which face the extracellular environment and the endosomal lumen, respectively [1]. In this issue of EMBO Reports, Hu and colleagues report that WD-repeat and FYVE-domain-containing protein 1 (WDFY1) recruits the signaling adaptor TRIF to TLR3 and TLR4, thereby potentiating signaling from these PRRs (Fig 1); [2].