SkiptomaincontentThankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtainthebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodeinInternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstylesandJavaScript.AdvertisementnaturenaturecommunicationsarticlesarticleLugduninamplifiesinnateimmuneresponsesintheskininsynergywithhost-andmicrobiota-derivedfactorsDownloadPDFSubjectsDiseasesImmunologyMicrobiologyAbstractRecentlyourgroupsdiscoveredlugdunin,anewcyclicpeptideantibioticthatinhibitsStaphylococcusaureusepithelialcolonizationinhumansandrodents.Inthiswork,weanalyzeditsimmuno-modulatoryandantimicrobialpotentialasasingleagentorincombinationwithothermicrobiota-orhost-derivedfactors.Weshowthatpretreatmentofprimaryhumankeratinocytesormouseskinwithlugduninincombinationwithmicrobiota-derivedfactorsresultsinasignificantreductionofS.aureuscolonization.Moreover,lugduninincreasesexpressionandreleaseofLL-37andCXCL8/MIP-2inhumankeratinocytesandmouseskin,andresultsintherecruitmentofmonocytesandneutrophilsinvivo,bothbyaTLR/MyD88-dependentmechanism.Interestingly,S.aureuseliminationbylugduninisadditionallyachievedbysynergisticantimicrobialactivitywithLL-37anddermcidin-derivedpeptides.Insummary,ourresultsindicatethatlugduninprovidesmulti-levelprotectionagainstS.aureusandmaythusbecomeapromisingtreatmentoptionforS.aureusskininfectionsinthefuture.DownloadPDFIntroductionSkinisachallenginghabitatforbacteriawithconditions,includingdryness,lownutrientavailability,highsaltconcentrations,andlowpH,aswellasthepresenceofhostantimicrobialpeptides(AMPs)andlipids1.Nevertheless,humanskinispopulatedbyacomplexmicrobiotawhosecompositionismainlydeterminedbytheecologicfeatureofthebodysite2,3,butisalsolargelyinfluencedbyhost-andbacteria-derivedfactors.Duringsteadystate,aconstantinterplayamongthemallowsforcolonizationwithcommensalmicroorganisms,whileatthesametimepathogenicmicroorganismssuchasStaphylococcusaureuscanbeeffici