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Science 17 September 1999:
Vol. 285. no. 5435, pp. 1917 - 1919
DOI: 10.1126/science.285.5435.1917
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Reports

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

Elena A. Levashina, 1*dagger Emma Langley, 1*ddagger Clare Green, 2 David Gubb, 2 Michael Ashburner, 2 Jules A. Hoffmann, 1 Jean-Marc Reichhart 1§

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 the spaetzle 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 in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.

1 UPR 9022 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 Rue René Descartes, Strasbourg 67084, France.
2 Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
*   These authors contributed equally to this study.

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

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

§   To whom correspondence should be addressed. E-mail: reichhart{at}ibmc.u-strasbg.fr

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