title: Rhizopus oryzae hyphae are damaged by human natural killer (NK) cells, but suppress NK cell mediated immunity.
abstract: Mucormycosis has a high mortality and is increasingly diagnosed in hematopoietic stem cell transplant (HSCT) recipients. In this setting, there is a growing interest to restore host defense to combat infections by adoptively transferring donor-derived immunocompetent cells. Natural killer (NK) cells exhibit antitumor and antiinfective activity, but the interaction with Mucormycetes is unknown. Our data demonstrate that both unstimulated and IL-2 prestimulated human NK cells damage Rhizopus oryzae hyphae, but do not affect resting conidia. The damage of the fungus is mediated, at least in part, by perforin. R. oryzae hyphae decrease the secretion of immunoregulatory molecules by NK cells, such as IFN-γ and RANTES, indicating an immunosuppressive effect of the fungus. Our data indicate that NK cells exhibit activity against Mucormycetes and future research should evaluate NK cells as a potential tool for adoptive immunotherapy in HSCT.
authors.affiliation: Pediatric Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Schmidt
authors.forename: Lars
authors.initials: L
authors.lastname: Tramsen
authors.forename: Susanne
authors.initials: S
authors.lastname: Perkhofer
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: Mitra
authors.initials: M
authors.lastname: Hanisch
authors.forename: Frauke
authors.initials: F
authors.lastname: Röger
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
mesh_terms: D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D025301:Hyphae / Q000502:physiology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D054353:Perforin / Q000235:genetics / Q000276:immunology; D012233:Rhizopus / Q000502:physiology*; D013172:Spores, Fungal / Q000502:physiology*
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D007376:Interleukin-2; D054353:Perforin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor