Inducible expression of double-stranded RNA reveals a role for dFADD in the regulation of the antibacterial response in Drosophila adults

Curr Biol. 2002 Jun 25;12(12):996-1000. doi: 10.1016/s0960-9822(02)00873-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Drosophila / genetics
  • Drosophila / immunology
  • Drosophila / microbiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology
  • Fas-Associated Death Domain Protein
  • Female
  • Gene Expression Regulation
  • Gram-Negative Bacteria / physiology
  • Insect Proteins / genetics
  • Male
  • RNA, Double-Stranded / biosynthesis


  • Adaptor Proteins, Signal Transducing
  • AttA protein, Drosophila
  • AttB protein, Drosophila
  • AttC protein, Drosophila
  • Carrier Proteins
  • DptA protein, Drosophila
  • Drosophila Proteins
  • Fas-Associated Death Domain Protein
  • Insect Proteins
  • RNA, Double-Stranded
  • attacin antibacterial protein, insect
  • imd protein, Drosophila
  • DRS protein, Drosophila