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An essential complementary role of NF-kappa B 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 
 EMBO JOURNAL, Vol.25(15) : 3693-3701, 2006 
Journal Title
Issue Date
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
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.
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5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Ryu, Ji Hwan(유지환)
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