An 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 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.
Ryu
Ji-Hwan
JH
Division of Molecular Life Science and National Creative Research Initiative Center for Symbiosystem, Ewha Woman's University, Seoul, South Korea.
Ha
Eun-Mi
EM
Oh
Chun-Taek
CT
Seol
Jae-Hong
JH
Brey
Paul T
PT
Jin
Ingnyol
I
Lee
Dong Gun
DG
Kim
Jaesang
J
Lee
Daekee
D
Lee
Won-Jae
WJ
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D029721:Drosophila Proteins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007113:Immunity, Innate / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C101626:Rel protein, Drosophila; D014157:Transcription Factors; C439909:imd protein, Drosophila