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

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 infec...

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Bibliographic Details
Published in:The EMBO journal 2006-08, Vol.25 (15), p.3693-3701
Main Authors: Ryu, J.H, Ha, E.M, Oh, C.T, Seol, J.H, Brey, P.T, Jin, I, Lee, D.G, Kim, J, Lee, D, Lee, W.J
Format: Article
Language:English
Subjects:
Animals
Antimicrobial Cationic Peptides - metabolism
Antimicrobial Cationic Peptides - pharmacology
antimicrobial peptides
disease resistance
Dose-Response Relationship, Drug
Drosophila - immunology
Drosophila - metabolism
Drosophila - microbiology
Drosophila melanogaster
Drosophila Proteins - metabolism
Escherichia coli
Gastrointestinal Tract - microbiology
immunity
Immunity, Innate - drug effects
infection
midgut
NF-kappa B - metabolism
reactive oxygen species
Reactive Oxygen Species - metabolism
Saccharomyces cerevisiae
Signal Transduction - drug effects
Time Factors
transcription factors
Transcription Factors - metabolism
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Summary: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.
ISSN:0261-4189
1460-2075