Drosophila MyD88 is an adapter in the Toll signaling pathway

Toll-like receptors comprise a family of cell surface receptors that play a crucial role in the innate immune recognition of both Drosophila and mamma ls. Previous studies have shown that Drosophila Toll-1 mediates the inducti on of antifungal peptides during fungal infection of adult flies. Through g enetic studies, Tube, Pelle, Cactus, and Dif have been identified as downst ream components of the Toll-1 signaling pathway. Here we report characteriz ation of a Drosophila homologue of human MyD88, dMyD88. We show that dMyD88 is an adapter in the Toll signaling pathway that associates with both the Toll receptor and the downstream kinase Pelle. Expression of dMyD88 in S2 c ells strongly induced activity of a Drosomycin reporter gene, whereas a dom inant-negative version of dMyD88 potently inhibited Toll-mediated signaling . We also show that dMyD88 associates with the death domain-containing adap ter Drosophila Fas-associated death domain-containing protein (dFADD), whic h in turn interacts with the apical caspase Dredd. This pathway links a cel l surface receptor to an apical caspase in invertebrate cells and therefore suggests that the Toll-mediated pathway of caspase activation may be the e volutionary ancestor of the death receptor-mediated pathway for apoptosis i nduction in mammals.