Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila

The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cac tus gene cassette, Here, a Loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to Lead to constitutiv e expression of the antifungal peptide drosomycin, and this effect was medi ated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteo lytic enzymes to its active Ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn4Ac-deficient flies. Hen ce, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defen se.