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

Ji Hwan Ryu, Eun Mi Ha, Chun Taek Oh, Jae Hong Seol, Paul T. Brey, Ingnyol Jin, Dong Gun Lee, Jaesang Kim, Daekee Lee, Won Jae Lee

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

In the Drosophila gut, reactive oxygen species (ROS)-dependent immunity is critical to host survival. This is in contrast to the NF-κB 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-κB/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-κB 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-κB pathway mutants in the intestine. These results imply that the local 'NF-κB/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.

Original languageEnglish
Pages (from-to)3693-3701
Number of pages9
JournalEMBO Journal
Volume25
Issue number15
DOIs
StatePublished - 9 Aug 2006

Keywords

  • Antimicrobial peptide
  • Drosophila
  • Gut innate immunity
  • NF-κB
  • Reactive oxygen species

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