Enhancement of neutrophil autophagy by an IVIG preparation against multidrug‐resistant bacteria as well as drug‐sensitive strains

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

关键词: xenophagy;    bactericidal activity;    phagocytosis;    NETs;   

DOI  :  10.1189/jlb.4A0813-422RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Autophagyoccursinhumanneutrophilsafterthephagocytosisofmultidrug‐resistantbacteriaanddrug‐sensitivestrains,includingEscherichiacoliandPseudomonasaeruginosa.ThepresentstudydetectedautophagybyimmunoblotanalysisofLC3Bconversion,byconfocalscanningmicroscopicexaminationofLC3Baggregateformationandbytransmissionelectronmicroscopicexaminationofbacteria‐containingautophagosomes.PatientswithseverebacterialinfectionsareoftentreatedwithIVIGalongsideantimicrobialagents.Here,weshowedthatIVIGinducedneutrophil‐mediatedphagocytosisofmultidrug‐resistantstrains.Comparedwithuntreatedneutrophils,neutrophilsexposedtoIVIGshowedincreasedlevelsofbacterialcellkilling,phagocytosis,O2−release,MPOrelease,andNETformation.IVIGalsoincreasedautophagyinthesecells.Inhibitingthelatephaseofautophagy(fusionoflysosomeswithautophagosomes)withbafilomycinA1‐reduced,neutrophil‐mediatedbactericidalactivity.Thesefindingsindicatethatautophagyplaysacriticalroleinthebactericidalactivitymediatedbyhumanneutrophils.Furthermore,theautophagosomeswithintheneutrophilscontainedbacteriaonlyandtheirorganellesonly,orbothbacteriaandtheirorganelles,apreviouslyundocumentedobservation.Takentogether,theseresultssuggestthatthecontentsofneutrophilautophagosomesmaybederivedfromspecificautophagicsystems,whichprovidetheneutrophilwithanadvantage.Thus,IVIGpromotestheneutrophil‐mediatedkillingofmultidrug‐resistantbacteriaaswellasdrug‐sensitivestrains...

【 授权许可】

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