Salmonella Transiently Reside in Luminal Neutrophils in the Inflamed Gut 英文参考文献.docVIP

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Salmonella Transiently Reside in Luminal Neutrophils in the Inflamed Gut 英文参考文献.doc

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SalmonellaTransientlyResideinLuminalNeutrophilsin theInflamedGut YvonneLoetscher1¤,AndreasWieser2,JetteLengefeld1,PatrickKaiser1,So¨renSchubert2, MathiasHeikenwalder3,Wolf-DietrichHardt1,Ba¨rbelStecher1,2* 1Institute of Microbiology, ETH Zu¨rich, Zu¨rich, Switzerland, 2Max von Pettenkofer Insititute, Ludwig Maximilians University Munich, Munich, Germany, 3Institute for Virology,TechnicalUniversityMunich/HelmholtzCenterMunich,Munich,Germany Abstract Background: Enteric pathogens need to grow efficiently in the gut lumen in order to cause disease and ensure transmission.Theinteriorofthegutformsacomplexenvironmentcomprisingthemucosalsurfaceareaandtheinnergut lumenwithepithelialcelldebrisandfoodparticles.Recruitmentofneutrophilstotheintestinallumenisahallmarkofnon- typhoidal Salmonella enterica infections in humans. Here, we analyzed the interaction of gut luminal neutrophils with S. entericaserovarTyphimurium(S.Tm)inamousecolitismodel. Results: Upon S. Tmwt infection, neutrophils transmigrate across the mucosa into the intestinal lumen. We detected amajorityof pathogensassociated withluminalneutrophils20 hoursafter infection. Neutrophils areviableandactively engulfS.Tm,asdemonstratedbylivemicroscopy.Using S.Tmmutantstrainsdefectiveintissueinvasionweshowthat pathogens are mostly taken up in the gut lumen at the epithelial barrier by luminal neutrophils. In these luminal neutrophils,S.Tminducesexpressionofgenestypicallyrequiredforitsintracellularlifestylesuchassiderophoreproduction iroBCDEandtheSalmonellapathogenicityisland2encodedtypethreesecretionsystem(TTSS-2).ThisshowsthatS.Tmat least transiently survives and responds to engulfment by gut luminal neutrophils. Gentamicin protection experiments suggestthatthelife-spanofluminalneutrophilsislimitedandthatS.Tmissubsequentlyreleasedintothegutlumen.This ‘‘fastcycling’’throughtheintracellularcompartmentofgutluminalneutrophilswouldexplainthehighfractionofTTSS-2 andiroBCDEexpressingintra-andextracellularbacteriainthel