Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: PMNs;    T cells;    IL‐;    17;   

DOI  :  10.1189/jlb.4A0214-092R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AlcoholicsareatincreasedriskofStaphylococcusaureusskininfectionandserioussequelae,suchasbacteremiaanddeath.DespitetheassociationbetweenalcoholismandsevereS.aureusskininfection,theimpactofEtOHonanti‐S.aureuscutaneousimmunityhasnotbeeninvestigatedinamodelofchronicEtOHexposure.TotestthehypothesisthatEtOHenhancestheseverityofS.aureusskininfection,micewerefedEtOHfor≥12weeksviatheMeadows‐CookmodelofalcoholismandinoculatedwithS.aureusfollowingepidermalabrasion.EvidenceofexacerbatedstaphylococcaldiseaseinEtOH‐fedmiceincluded:skinlesionsthatwerelargerandcontainedmoreorganisms,greaterweightloss,andincreasedbacterialdissemination.InfectedEtOH‐fedmicedemonstratedpoormaintenanceandinductionofPMNresponsesinskinanddrainingLNs,respectively.Additionally,alteredPMNdynamicsintheskinofthesemicecorrespondedwithreducedproductionofIL‐23andIL‐1βbyCD11b+myeloidcellsandIL‐17productionbyγδTcells,withthelatterdefectoccurringinthedrainingLNsaswell.Inaddition,IL‐17restorationattenuatedS.aureus‐induceddermatopathologyandimprovedbacterialclearancedefectsinEtOH‐fedmice.Takentogether,thefindingsshow,inanovelmodelsystem,thattheEtOH‐inducedincreaseinS.aureus‐relatedinjury/illnesscorrespondswithdefectsintheIL‐23/IL‐17inflammatoryaxisandpoorPMNaccumulationatthesiteofinfectionanddrainingLNs.ThesefindingsoffernewinformationabouttheimpactofEtOHoncutaneoushost‐defensepathwaysandprovideapotentialmechanismexplainingwhyalcoholicsarepredisposedtoS.aureusskininfection...

【 授权许可】

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