Constitutive Activation of Toll-Mediated Antifungal Defense in Serpin-Deficient Drosophila

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Science  17 Sep 1999:
Vol. 285, Issue 5435, pp. 1917-1919
DOI: 10.1126/science.285.5435.1917

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The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by thespaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present inSpn43Ac-deficient flies. Hence, Spn43Acnegatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophilahost defense.

  • * These authors contributed equally to this study.

  • Present address: European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 67117, Germany.

  • Present address: Wellcome/CRC Institute, Tennis Court Road, Cambridge CB2 1QR, UK.

  • § To whom correspondence should be addressed. E-mail: reichhart{at}

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