title: Aspergillus fumigatus responds to natural killer (NK) cells with upregulation of stress related genes and inhibits the immunoregulatory function of NK cells.
abstract: Natural Killer (NK) cells are active against Aspergillus fumigatus, which in turn is able to impair the host defense. Unfortunately, little is known on the mutual interaction of NK cells and A. fumigatus. We coincubated human NK cells with A. fumigatus hyphae and assessed the gene expression and protein concentration of selected molecules. We found that A. fumigatus up-regulates the gene expression of pro-inflammatory molecules in NK cells, but inhibited the release of these molecules resulting in intracellular accumulation and limited extracellular availability. A. fumigatus down-regulatedmRNA levels of perforin in NK cells, but increased its intra- and extracellular protein concentration. The gene expression of stress related molecules of A. fumigatus such as heat shock protein hsp90 was up-regulated by human NK cells. Our data characterize for the first time the immunosuppressive effect of A. fumigatus on NK cells and may help to develop new therapeutic antifungal strategies.
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 Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Blatzer
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Posch
authors.affiliation: Division of Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, 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: 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: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
mesh_terms: D001232:Aspergillus fumigatus / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D018841:HSP90 Heat-Shock Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Immune response; Immunity; Immunology and Microbiology Section; cytokine; gene expression; human natural killer cell; perforin; Aspergillus fumigatus