SinceamajorcomplicationofUTIsisfrequentrecurrence,thereappearstobeafatefuldefect intheurinaryimmunesystem.Adistinctfeatureofthebladderwhichappearstocontributeto theirsusceptibilitytoreinfectionisthehighdegreeofatypicaltissueremodelingthatoccurs followingeachinfection,predisposingthebladdertofutureinfections.Sinceverylittleis currentlyknownregardingbladderremodeling,studiesonthistopicmayrevealnewstrategies tocombatrecurrentUTIs.Wehavehypothesizedthatbecauseofthehighlycytotoxicand hyperosmolarnatureofurine,thebladderinitiatesavigorousre-epithelizationandremodeling programtorapidlyrecoverlostepitheliumaftereachinfection.Ourpreliminarystudieshave validatedthisnotionandrevealedthatTcellsrecruitedintothebladderaremorespecializedin directingtissuerepair(Th2)thaninpathogenelimination(Th1).Consequently,theinfecting bacteriainthebladderarenotcompletelyeliminatedfollowingresolutionofinfection, predisposingthisorgantofutureflare-ups.SincethetissuerepairTcellsrecruitedintothe bladdertendtopersistandcouldbequicklyevokedwithreinfection,themagnitudeofthe remodelingprogramishigh,significantlyimpactingbladdervoidingcapacity.Wehavefound thatacriticalimmuneregulatorassociatedwiththebladderrepairprogramisadistinctsubclass ofdendriticcells(DCs),whichmovesintothesubepithelialregionofthebladdersoonafterthe lossofthesuperficialepithelium.Here,weproposetodeterminethespecificroleofthisDC subclassinepithelialrepair.WewillalsoexaminetheunderlyingbasisfortheTh2biasofT cellsrecruitedintothebladderfollowingboutsofinfection.Finally,wewillinvestigatethe possibilityofreprogramingTh2primedbladderresponseintoaTh1typeresponseby immunizingnaveandchronicallyinfectedmicewithavaccineantigenco-administeredwithTh1 biasingadjuvant.Wesuspectthatsuchvaccineswillnotonlyprotectbladderfromfuture infectionbutalsopermitrecoveryofbladderfunctioninthesemice
NIH ExPorter
NIH ExPorter