An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity

EMBO J. 2006 Aug 9;25(15):3693-701. doi: 10.1038/sj.emboj.7601233. Epub 2006 Jul 20.


In the Drosophila gut, reactive oxygen species (ROS)-dependent immunity is critical to host survival. This is in contrast to the NF-kappaB pathway whose physiological function in the microbe-laden epithelia has yet to be convincingly demonstrated despite playing a critical role during systemic infections. We used a novel in vivo approach to reveal the physiological role of gut NF-kappaB/antimicrobial peptide (AMP) system, which has been 'masked' in the presence of the dominant intestinal ROS-dependent immunity. When fed with ROS-resistant microbes, NF-kappaB pathway mutant flies, but not wild-type flies, become highly susceptible to gut infection. This high lethality can be significantly reduced by either re-introducing Relish expression to Relish mutants or by constitutively expressing a single AMP to the NF-kappaB pathway mutants in the intestine. These results imply that the local 'NF-kappaB/AMP' system acts as an essential 'fail-safe' system, complementary to the ROS-dependent gut immunity, during gut infection with ROS-resistant pathogens. This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Antimicrobial Cationic Peptides / pharmacology
  • Dose-Response Relationship, Drug
  • Drosophila / immunology*
  • Drosophila / metabolism
  • Drosophila / microbiology*
  • Drosophila Proteins / metabolism
  • Gastrointestinal Tract / microbiology*
  • Immunity, Innate / drug effects
  • NF-kappa B / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction* / drug effects
  • Time Factors
  • Transcription Factors / metabolism


  • Antimicrobial Cationic Peptides
  • Drosophila Proteins
  • NF-kappa B
  • Reactive Oxygen Species
  • Rel protein, Drosophila
  • Transcription Factors
  • imd protein, Drosophila