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
Statement: A distinct feature of the bladder is its increased susceptibility to reinfection which appears to grow with each infection. We have attributed this phenomenon to preferential recruitment into the bladder of cells specialized in tissue repair over cells that are capable of eliminating pathogens, which leaves this organ prone to reinfection. Our goal here is to examine the basis for this aberrant response and to device a preventive vaccination strategy.