Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis Balázs Rada.pdf

该【Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis Balázs Rada 】是由【四婆子】上传分享，文档一共【24】页，该文档可以免费在线阅读，需要了解更多关于【Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis Balázs Rada 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。:..pathogensReviewInteractionsbetweenNeutrophilsandPseudomonasaeruginosainCysticFibrosisBalázsRadaCollegeofVeterinaryMedicine,DepartmentofInfectiousDiseases,ia,,Athens,GA30602,USA;******@;Tel.:+1-706-5423695;Fax:+1-706-5425771AcademicEditor::23December2016;Accepted:3March2017;Published:9March2017Abstract:Cystic?brosis(CF)affects70,,microbialinfectionsandchronicin??brosisairwayin?ammationismediatedbyrobustin?ltrationofpolymorphonuclearneutrophilgranulocytes(PMNs,neutrophils).,-:Pseudomonasaeruginosa;cystic?brosis;neutrophil;neutrophilextracellulartraps;bio?lm;?agellum;phagocytosis;oxidative;,anOpportunisticPathogenurrenceinaqueousenvironmentsinnature[1,2].Thisubiquitous,Gram-negativepathogenhasalargegenomethatenablesitsadaptationtodiversegrowthconditionsandinfectionsinmanyspecies,rangingfromnematodestovertebrates,includinghumans[3,4].[3].,differentgrowthforms,asplanktonicbacteriaandbio?lms[5].Planktonicbacteriaharborseveralsurfaceappendagesthatmediatemotility(?agellum,pilus)andvirulence(secretionsystems)[6,7].[8–10].?lmsissohighthatthisbacteriumbecameanismformicrobialbio?,??(18%–20%)iallunginfections(alsocalledhospital-acquiredorhealthPathogens2017,6,10;doi::..Pathogens2017,6,102of24care-associatedpneumonia)[11–14].promisedpatients,bio?,urrenceofmultidrug-resistantstrainsinhospitalwardsandhealthcarepersonnelcarryingthisbacterium[15–18].[19].[20,21].Susceptibilityofhumanimmunode?ciencyvirus(HIV);8%–25%ofHIVpatientswithpneumoniaareinfectedwiththisbacterium[14].Chronicobstructivepulmonarydisease(COPD)(4%–15%ofadultCOPDpatients)andpresentdiversesymptomsrangingfrommildbronchitistopneumoniawithsepsis[22–24].Inadditiontothetransientinfectionsmentionedabove,,suchasinpatientswithcystic?brosis(CF),non-CFbronchiectasisandprimaryciliarydyskinesia(PCD).AlthoughmoreprevalentthanCF,lessisknownaboutthediverseetiologiesofnon--CFbronchiectasispatientstypicallydeveloppermanentdamageanisms,,despiteanyobviousabnormalitiesintheirimmunesystem[24].PCDischaracterizedbyimpairedmucociliaryclearanceoftheairwaysthatpreventsmucustransportandenablespersistentinfectionswithbacteria,[25].,,000peopleworldwide[26].Mutationsinthecystic?brosistransmembraneregulator(CFTR)anionchannelalternormalionand?uidtransportacrosstheairwayepithelium,leadtothickenedmucusformation,impairedmucociliaryclearance,bacterialadherenceandin?ammation[26,27].Theviciouscycleofimpairedclearance-infection-in?ammationdriveslong-termlungdamage,bronchiectasis,air?owobstructionanddeathinCF[27].Inthelungs,CFTRisprimarilyexpressedinepithelialcells,andthisde??rstthatdrivessubsequentin?ammationortheepithelialCFTRdefecttriggersahyperin?-developedpiganimalmodelofCFlungdiseasestartedtoclarifysomeoftheseunansweredquestions[28].AlthoughCFlungshostpolymicrobialinfections,[26,27,29].Accordingtothe2015CysticFibrosisFoundationPatientRegistryAnnualDataReport,,,,-[30–32].[33].ItspersistenceintheCFlungisthoughttobeduelargelytoitsabilitytoformbio?lms[34–36].Inbio?lms,-haridealginate[36].?lmsalsocontainself-producedorforeignDNAinCFairways[36].Bio?,characterizedbyhighmotilityand?agellumexpression[37](Figure1).The??agellum-de?cientstrainsareseverelyreducedinvirulence[38,39].Ontheotherhand,overthecourseofCFinfection,?agellarmotility[33,37](Figure1).,alginateproduction,adecreaseinvirulencefactorexpressionandbio?lm:..Pathogens2017,6,103of24Pathogens2017,6,103of23formation[37].[40].The?agellumisbiofilmformation[37].[40].Thealsoneededtoinitiatebio?[41,42].InchronicstagesofCFairwaydisease,[41,42].??lmculturesareresistantagainsttheairwaydisease,,includingantibiotics,andensurelong-termresistantagainsttheattacksoftheimmunesystemandmedicaltreatments,includingantibiotics,,ensurelong-,?lms[8,43–46].[8,43–46].?cientlyeliminatedbytheimmunesystem,particularlyneutrophilsthatarepresentandwhyitisnotefficientlyeliminatedbytheimmunesystem,particularlyneutrophilsthatareinlargenumbersanddrivein?ammation[31].presentinlargenumbersanddriveinflammation[31].(PMNs)plexinteractionsbetweenpolymorphonuclearneutrophilgranulocytesand(PMNsPseudomonasaeruginosa)andPseudomonasaeruginosaincystic?brosis(CF)airwayswithaspecialemphasisonneutrophilincysticfibrosis(CF)airwayswithaspecialemphasisons).ROS:).ROS:(chemotherapy,HIV)[numbers(chemotherapy,HIV)14,20,[14,20,21]21].Humansde?cientinkeyneutrophil--mediatedmechanisms,suchasspeci?cgranulede?ciencyorleukocyteadhesionde?ciency,oantimicrobialmechanisms,suchasspecificgranuledeficiencyorleukocyteadhesiondeficiency,[47infection].PMNdepletioninmiceleadstoenhancedmortalityinacute[47].[48,49].Inneutropenicmice5,a105-timessmallerdoseoflunginfectionmodels[48,49].Inneutropenicmice,a10-[].normalPMNnumbers[48].Similareffectswereshowninrabbits,aswell[50].AirwayepithelialSimilareffectswereshowninrabbits,aswell[50].AirwayepithelialcontrolofPMNin??[51,52].Theantimicrobialpeptideairways[51,52].TheantimicrobialpeptideLL-37,highlyexpressedinPMNs,alsoaugmentsLL-37,highlyexpressedinPMNs,[53,54].Overall,[,54].Overall,?.:..Pathogens2017,6,?ltrationthatisdrivenbychemoattractantmoleculesprimarilyreleasedbyairwayepithelialcellsoralreadyrecruitedleukocytes,(IL-8)isoneofthemostpotentPMN-recruitingchemokinesthatcanbereleasedbyepithelialcells,PMNsandmacrophagesandisrecognizedbytwochemokinereceptors,CXCR1andCXCR2(C-X-Cmotifchemokinereceptor1and2)[55].ConcentrationsofIL-8inCFairwaysiselevatedandcorrelatedwithlungdamage[56–59].ElevatedsputumIL-[60].IL-8isalsodetectedintheexhaledbreathcondensateofCFpatients,[61].PMNsandmacrophagescanbemajorsourcesofIL-8inCFsincebothphagocytesreleaseIL-haride(LPS)andhoststimuli(IL-1,TNF-)[62].AirwayepithelialcellsreleaseIL-,LPSoritsextracellularpigmentpyocyanin[63–66].PMNelastasepresentinCFairway?uidshasalsobeenshowntoinduceIL-8releaseinairwayepithelialcells[67].InadditiontoIL-8releasestimulatedbyexogenousmicrobialorhoststimuli,enhancedendogenousIL-8productionhasalsobeenproposedtodriveearlyin?-de?cientairwayepithelialcellssecretelargeramountsofIL-8thantheirwild-typecounterparts,indicatinganepithelium-derivedproin?ammatoryeffectofIL-8inCF[68–70].EndoplasmicreticulumstressandexaggeratedNF-BactivationinducedbymisfoldedCFTRisthelikelyreasonforenhancedchemokineproductioninCFepithelialcells[71–73].AmongthemanypotentialPMN-recruitingmoleculespresentintheCFsputum[74],[75].FormationofC5ahasbeendemonstratedinCFairway?uids[76].WhetherC5aisamainPMNrecruiterinCFairwaysremainstobeelucidatedasPMNserineproteasesweresuggestedtodegradeandinactivatetheC5areceptoronPMNs[77].Althoughnotaspotentasthepreviousmolecules,theproin?a