Inducible expression of double-stranded RNA reveals a role for dFADD in the regulation of the antibacterial response in Drosophila adults.
In Drosophila, the immune deficiency (Imd) pathway controls antibacterial peptide gene expression in the fat body in response to Gram-negative bacterial infection. The ultimate target of the Imd pathway is Relish, a transactivator related to mammalian P105 and P100 NF-kappaB precursors. Relish is processed in order to translocate to the nucleus, and this cleavage is dependent on both Dredd, an apical caspase related to caspase-8 of mammals, and the fly Ikappa-B kinase complex (dmIKK). dTAK1, a MAPKKK, functions upstream of the dmIKK complex and downstream of Imd, a protein with a death domain similar to that of mammalian receptor interacting protein (RIP). Finally, the peptidoglycan recognition protein-LC (PGRP-LC) acts upstream of Imd and probably functions as a receptor for the Imd pathway. Using inducible expression of dFADD double-stranded RNA, we demonstrate that dFADD is a novel component of the Imd pathway: dFADD double-stranded RNA expression reduces the induction of antibacterial peptide-encoding genes after infection and renders the fly susceptible to Gram-negative bacterial infection. Epistatic studies indicate that dFADD acts between Imd and Dredd. Our results reinforce the parallels between the Imd and the TNF-R1 pathways.
Leulier
François
F
Centre de Génétique Moléculaire, CNRS, 91198 Gif-sur-Yvette, France.
Vidal
Sheila
S
Saigo
Kaoru
K
Ueda
Ryu
R
Lemaitre
Bruno
B
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D053200:Fas-Associated Death Domain Protein; D005260:Female; D005786:Gene Expression Regulation; D006090:Gram-Negative Bacteria / Q000502:physiology; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D012330:RNA, Double-Stranded / Q000096:biosynthesis
D048868:Adaptor Proteins, Signal Transducing; C488990:AttA protein, Drosophila; C488991:AttB protein, Drosophila; C488989:AttC protein, Drosophila; D002352:Carrier Proteins; C054756:DptA protein, Drosophila; D029721:Drosophila Proteins; D053200:Fas-Associated Death Domain Protein; D019476:Insect Proteins; D012330:RNA, Double-Stranded; C039711:attacin antibacterial protein, insect; C439909:imd protein, Drosophila; C091227:DRS protein, Drosophila