AIMTotestwhetherNox1playsaroleintyphlitisinducedbySalmonellaentericaserovarTyphimurium(S.Tm)inamousemodel.METHODSEight-week-oldmalewild-type(WT)andNox1knockout(KO)C57BL6/J(B6)micewereadministeredmetronidazolewaterfor4dtomakethemsusceptibletoS.Tminfectionbytheoralroute.Themiceweregivenplainwaterandadministeredwith4differentdosesofS.Tmbyoralgavage.Themicewerefollowedforanother4d.Fromthetimeofthemetronidazoleapplication,themicewereobservedtwicedailyandweigheddaily.Theileum,cecumandcolonwereremovedforsamplingatthefourthdaypost-inoculation.PortionsofallthreetissueswerefixedforhistologyandplacedinRNAlaterformRNA/cDNApreparationandquantitativereal-timePCR.ThecontentsofthececumwererecoveredforestimationofS.TmCFU.RESULTSWefoundNox1-knockout(Nox1-KO)micewerenotmoresensitivetoS.TmcolonizationandinfectionthanWTB6mice.Thisconclusionisbasedonthefollowingobservations:(1)S.Tm-infectioninducedsimilarweightlossinNox1-KOmicecomparedtoWTmice;(2)thesameS.TmCFUwasrecoveredfromthececalcontentofNox1-KOandWTmiceregardlessoftheinoculationdose,exceptthelowestinoculationdose(2×106CFU)forwhichtheNox1-KOhadone-loglowerCFUthanWTmice;(3)thereisnodifferenceincecalpathologybetweenWTandNox1-KOgroups;and(4)therearenoS.Tminfection-inducedchangesingeneexpressionlevels(IL-1b,TNF-α,andDuox2)betweenWTandNox1-KOgroups.TheAlpigeneexpressionwasmoresuppressedbyS.TmtreatmentinWTthantheNox1-KOcecum.CONCLUSIONNox1doesnotprotectmicefromS.Tmcolonization.Nox1-KOprovidesaveryminorprotectiveeffectagainstS.Tminfection.UsingNOX1-specificinhibitorsforcolitistherapyshouldnotincreaserisksinbacterialinfection.
