title: Human natural killer cells acting as phagocytes against Candida albicans and mounting an inflammatory response that modulates neutrophil antifungal activity.
abstract: BACKGROUND
  Natural killer (NK) cells are innate lymphocytes with potent cytotoxic activity. Whereas activity of NK cells has been demonstrated against the fungal pathogens Aspergillus fumigatus and Cryptococcus neoformans, little was known about their interaction with Candida albicans.
  
  
  METHODS
  Primary human NK cells were isolated from buffy coats, primed with a cytokine cocktail and used for confrontation assays with C. albicans. Interaction was monitored and quantified using live cell imaging, confocal microscopy, flow cytometry, and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Human NK cells actively recognized C. albicans, resulting in degranulation and secretion of granulocyte-macrophage colony-stimulating factor, interferon γ, and tumor necrosis factor α . Uniquely, activation of NK cells was triggered by actin-dependent phagocytosis. Antifungal activity of NK cells against C. albicans could be detected and mainly attributed to secreted perforin. However, NK cells were unable to inhibit filamentation of C. albicans. Human polymorphonuclear neutrophils (PMNs) counteracted the proinflammatory reaction of NK cells by preventing direct contact between NK cells and the fungal pathogen. Activation of PMNs was enhanced in the presence of NK cells, resulting in increased fungicidal activity.
  
  
  CONCLUSIONS
  Our results show a unique pattern of NK cell interaction with C. albicans, which involves direct proinflammatory activation and modulation of PMN activity. For the first time, phagocytosis of a pathogen is shown to contribute to NK cell activation.
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute.
authors.forename: Jessica
authors.initials: J
authors.lastname: Voigt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hünniger
authors.forename: Maria
authors.initials: M
authors.lastname: Bouzani
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.forename: Dagmar
authors.initials: D
authors.lastname: Barz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000276:immunology*; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*
chemical_list: D016207:Cytokines; D054353:Perforin
keywords: C. albicans; IFN-γ; NK cells; TNF-α; neutrophils; perforin; phagocytosis