A large-scale RNAi screen identifies Deaf1 as a regulator of innate immune responses in Drosophila.
Innate immune signalling pathways are evolutionarily conserved between invertebrates and vertebrates. The analysis of NF-kappaB 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-kappaB 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-kappaB factors Dorsal and Dif. These results indicate that Deaf1 is an important contributor to innate immune responses in vivo.
Kuttenkeuler
David
D
German Cancer Research Center (DKFZ) and University of Heidelberg, Division of Signaling and Functional Genomics, University of Heidelberg, Heidelberg, Germany.
Pelte
Nadège
N
Ragab
Anan
A
Gesellchen
Viola
V
Schneider
Lena
L
Blass
Claudia
C
Axelsson
Elin
E
Huber
Wolfgang
W
Boutros
Michael
M
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000254:growth & development / Q000276:immunology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017344:Genes, Insect; D023281:Genomics; D007113:Immunity, Innate; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C485477:Deaf1 protein, Drosophila; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C091227:DRS protein, Drosophila