Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections 英文参考文献.docVIP

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Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections 英文参考文献.doc

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Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections 英文参考文献

Short-TermStarvationofImmuneDeficientDrosophila ImprovesSurvivaltoGram-NegativeBacterialInfections AnthonyE.Brown1,2,JaninaBaumbach1,PeterE.Cook2,PetrosLigoxygakis1* 1GeneticsUnitDepartmentofBiochemistry,UniversityofOxford,Oxford,UnitedKingdom,2PeterMedawarBuildingforPathogenResearch,UniversityofOxford,Oxford, UnitedKingdom Abstract Background: Primary immunodeficiencies are inborn errors of immunity that lead to life threatening conditions. These predispositionsdescribehumanimmunityinnaturaandhighlighttheimportantfunctionofcomponentsoftheToll-IL-1- receptor-nuclear factor kappa B (TIR-NF-kB) pathway. Since the TIR-NF-kB circuit is a conserved component of the host defenceinhigheranimals,geneticallytractablemodelsmaycontributeideasforclinicalinterventions. Methodology/Principal Findings: We used immunodeficient fruit flies (Drosophila melanogaster) to address questions pertaining to survival following bacterial infection. We describe here that flies lacking the NF-kB protein Relish, indispensableforcounteringGram-negativebacteria,hadagreatlyimprovedsurvivaltosuchinfectionswhensubjectto dietary short-term starvation (STS) prior to immune challenge. STS induced the release of Nitric Oxide (NO), a potent moleculeagainstpathogensinflies,miceandhumans.AdministeringtheNOSynthase-inhibitoryarginineanalogN-Nitro-L- Arginine-Methyl-Ester (L-NAME) but not its inactive enantiomer D-NAME increased once again sensitivity to infection to levelsexpectedforrelishmutants.Surprisingly,NOsignallingrequiredtheNF-kBproteinDif,usuallyneededforresponses againstGram-positivebacteria. Conclusions/Significance: OurresultsshowthatNOreleasethroughSTSmayreflectanevolutionaryconservedprocess. Moreover,STScouldbeexploredtoaddressimmunephenotypesrelatedtoinfectionandmayofferwaystoboostnatural immunity. Citation: Brown AE, Baumbach J, Cook PE, Ligoxygakis P (2009) Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative BacterialInfections.PLoSONE4(2):e4490.doi:10.1