Salmonella Induced IL-23 and IL-1β Allow for IL-12 Production by Monocytes and Mφ1 through Induction of IFN-γ in CD56+ NKNK-Like T Cells 英文参考文献.docVIP

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Salmonella Induced IL-23 and IL-1β Allow for IL-12 Production by Monocytes and Mφ1 through Induction of IFN-γ in CD56+ NKNK-Like T Cells 英文参考文献.doc

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SalmonellaInducedIL-23andIL-1bAllowforIL-12 ProductionbyMonocytesandMQ1throughInductionof IFN-cinCD56+NK/NK-LikeTCells DiederikvandeWetering,RoelofA.dePaus,JaapT.vanDissel,EsthervandeVosse* DepartmentofInfectiousDiseases,LeidenUniversityMedicalCenter,Leiden,TheNetherlands Abstract Background:Thetype-1cytokinepathwayplaysapivotalroleinimmunityagainstintracellularbacterialpathogenssuchas Salmonellae and Mycobacteria. Bacterial stimulation of pattern recognition receptors on monocytes, macrophages and dendritic cells initiates this pathway, and results in the production of cytokines that activate lymphocytes to produce interferon(IFN)-c.Interleukin(IL)-12andIL-23arethoughttobethekeycytokinesrequiredforinitiatingatype-1cytokine immuneresponsetoMycobacteriaandSalmonellae.TherelativecontributionofIL-23andIL-12tothisprocessisuncertain. Methodology/PrincipalFindings:WeshowthatvariousTLRagonistsinducetheproductionofIL-23butnotIL-12infreshly isolated human monocytes and cultured human macrophages. In addition, type 1 pro-inflammatory macrophages (MQ1) differentiated in the presence of GM-CSF and infected with live Salmonella produce IL-23, IL-1b and IL-18, but not IL-12. SupernatantsofSalmonella-infectedMQ1containedmoreIL-18andIL-1bascomparedwithsupernatantsofMQ1stimulatedwith isolated TLR agonists, and induced IFN-c production in human CD56+ cells in an IL-23 and IL-1b-dependent but IL-12- + independentmanner.Inaddition,IL-23togetherwithIL-18orIL-1bledtotheproductionofGM-CSFinCD56 cells.BothIFN-c andGM-CSFenhancedIL-23productionbymonocytesinresponsetoTLRagonists,aswellasinducedIL-12production. Conclusions/Significance: The findings implicate a positive feedback loop in which IL-23 can enhance its release via inductionofIFN-candGM-CSF.TheIL-23inducedcytokinesallowforthesubsequentproductionofIL-12andamplifythe IFN-cproductioninthetype-1cytokinepathway. Citation:vandeWeteringD,dePausRA,vanDisselJT,vandeVosseE(2009)SalmonellaInducedIL-23andIL-1bAllowforIL-12Productionby