title: Human natural killer cells exhibit direct activity against Aspergillus fumigatus hyphae, but not against resting conidia.
abstract: Because natural killer (NK) cells kill tumor cells and combat infections, there is growing interest in adoptively transferring NK cells to hematopoietic stem cell recipients. Unfortunately, in humans, the activity of NK cells against Aspergillus species, the major cause of invasive fungal infection in stem cell recipients, are poorly characterized. Our results show that unstimulated and interleukin-2 prestimulated human NK cells kill Aspergillus fumigatus hyphae but do not affect resting conidia. Killing is also induced by the supernatant of prestimulated NK cells and human perforin. The high levels of interferon-γ and granulocyte macrophage colony-stimulating factor produced by prestimulated NK cells are significantly reduced by Aspergillus, indicating an immunosuppressive effect of the fungus. Whereas Aspergillus hyphae activate NK cells, resting, and germinating, conidia and conidia of ΔrodA mutants lacking the hydrophobic surface layer do not. Our results suggest that adoptively transferred human NK cells may be a potential antifungal tool in the transplantation context.
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: Mitra
authors.initials: M
authors.lastname: Hanisch
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
authors.forename: Sabine
authors.initials: S
authors.lastname: Huenecke
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
mesh_terms: D001232:Aspergillus fumigatus / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D025301:Hyphae / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D013172:Spores, Fungal / Q000276:immunology / Q000502:physiology*
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D007376:Interleukin-2; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor