A Large-Scale RNAi Screen Identifies Deaf1 as a Regulator of Innate Immune Responses in DrosophilaKuttenkeuler D. · Pelte N. · Ragab A. · Gesellchen V. · Schneider L. · Blass C. · Axelsson E. · Huber W. · Boutros M.
aGerman Cancer Research Center (DKFZ) and University of Heidelberg, Division of Signaling and Functional Genomics, University of Heidelberg, Heidelberg, Germany; bEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK
Innate immune signalling pathways are evolutionarily conserved between invertebrates and vertebrates. The analysis of NF-ĸB signalling in Drosophila has contributed important insights into how organisms respond to infection. Nevertheless, significant gaps remain in our understanding of how the activation of intracellular signalling elicits specific transcriptional programs. Here we report a genome-wide RNA interference survey for transcription factors that are required for Toll-dependent immune responses. In addition to the NF-ĸB homologs Dif, Dorsal and factors of the general transcription machinery, we identified Deformed Epidermal Autoregulatory Factor 1 (Deaf1) to be required for the expression of the Toll target gene Drosomycin in cultured cells and in Drosophila in vivo. We show that Deaf1 is required for the survival of flies after fungal, but not E. coli, infection. We determine that Deaf1 acts downstream of the NF-ĸB factors Dorsal and Dif. These results indicate that Deaf1 is an important contributor to innate immune responses in vivo.
Prof. Dr. Michael Boutros
German Cancer Research Center (DKFZ) and University of Heidelberg
Im Neuenheimer Feld 580
DE–69120 Heidelberg (Germany)
Tel. +49 6221 42 1951, Fax +49 6221 42 1959, E-Mail email@example.com
D.K., N.P. and A.R. contributed equally to this paper.
Received: May 8, 2009
Accepted after revision: August 10, 2009
Published online: October 13, 2009
Number of Print Pages : 14
Number of Figures : 5, Number of Tables : 0, Number of References : 47
Journal of Innate Immunity
Vol. 2, No. 2, Year 2010 (Cover Date: February 2010)
Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)
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