title: Natural killer cell-mediated damage of clinical isolates of mucormycetes.
abstract: Haematopoietic stem cell transplant (HSCT) recipients are at high risk for mucormycosis, which has a mortality of up to 90%. The adoptive transfer of Natural killer (NK) cells is a promising therapeutic option in order to improve the reconstitution of host immunity after HSCT and to directly combat the fungal pathogen. As a number of fungal pathogens have developed strategies to evade the innate immune system, we investigated the interaction of human NK cells with various clinical isolates of different species of mucormycetes. Our results show that human IL-2 prestimulated NK cells damaged all mucormycetes tested. The extent of the damage depended, at least in part, on the growth curve characteristics of the individual fungal isolate. All isolates decreased the secretion of interferon-γ by NK cells to a similar extent. Our data suggest that NK cells damage a wide spectrum of mucormycetes, but that the antifungal effect is higher if NK cells are administered at an early time point of infection.
authors.affiliation: Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Asuman
authors.initials: A
authors.lastname: Demir
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
mesh_terms: D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D009089:Mucor / Q000276:immunology / Q000302:isolation & purification; D009090:Mucorales / Q000276:immunology* / Q000302:isolation & purification; D009091:Mucormycosis / Q000382:microbiology; D012233:Rhizopus / Q000276:immunology / Q000302:isolation & purification
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Invasive fungal disease; antifungal activity; immunomodulation; mucormycetes; natural killer cells