title: Protection of Candida parapsilosis from neutrophil killing through internalization by human endothelial cells.
abstract: Candida parapsilosis is a fungal pathogen that is associated with hematogenously disseminated disease in premature neonates, acutely ill or immunocompromised patients. In cell culture, C. parapsilosis cells are actively and avidly endocytosed by endothelial cells via actin polymerization mediated by N-WASP. Here we present evidence that C. parapsilosis that were internalized by endothelial cells remained alive, and avoided being acidified or otherwise damaged via the host cell. Internalized fungal cells reproduced intracellularly and eventually burst out of the host endothelial cell. When neutrophils were added to endothelium and C. parapsilosis, they patrolled the endothelial surface and efficiently killed most adherent fungal cells prior to endocytosis. But after endocytosis by endothelial cells, internalized fungal cells evaded neutrophil killing. Silencing endothelial N-WASP blocked endocytosis of C. parapsilosis and left fungal cells stranded on the cell surface, where they were susceptible to neutrophil killing. These observations suggest that for C. parapsilosis to escape from the bloodstream, fungi may adhere to and be internalized by endothelial cells before being confronted and phagocytosed by a patrolling leukocyte. Once internalized by endothelial cells, C. parapsilosis may safely replicate to cause further rounds of infection. Immunosurveillance of the intravascular lumen by leukocytes crawling on the endothelial surface and rapid killing of adherent yeast may play a major role in controlling C. parapsilosis dissemination and infected endothelial cells may be a significant reservoir for fungal persistence.
authors.affiliation: a Department of Pediatrics; Women & Infants Hospital of Rhode Island ; Providence , RI , USA.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Glass
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Longley
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Bliss
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Shaw
mesh_terms: D000268:Adhesiveness; D002175:Candida / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity* / Q000648:ultrastructure; D002478:Cells, Cultured; D004705:Endocytosis; D042783:Endothelial Cells / Q000382:microbiology* / Q000502:physiology / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
keywords: Candida; HUVEC, Human Umbilical Vein Endothelial Cells; N-WASP, Neuronal Wiskott-Aldrich Syndrome protein; NETs, Neutrophil Extracellular Traps; PMN, Polymorphonuclear leukocytes; YPD, Yeast Peptone Dextrose medium; endocytosis; endothelium; neutrophils; phagocytosis