The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults.
The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.
Lemaitre
B
B
Institut de Biologie Moléculaire at Cellulaire, UPR 9022 du Centre National de la Recherche Scientifique, Strasbourg, France.
Nicolas
E
E
Michaut
L
L
Reichhart
J M
JM
Hoffmann
J A
JA
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D029721:Drosophila Proteins; D005658:Fungi / Q000276:immunology; D015870:Gene Expression; D017344:Genes, Insect; D005802:Genes, MHC Class II; D007301:Insect Hormones / Q000235:genetics; D019476:Insect Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D009181:Mycoses / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051193:Toll-Like Receptors
D000935:Antifungal Agents; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010750:Phosphoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C086179:spz protein, Drosophila; C077938:cact protein, Drosophila; C091227:DRS protein, Drosophila