title: Human NK cells display important antifungal activity against Aspergillus fumigatus, which is directly mediated by IFN-γ release.
abstract: Despite the strong interest in the NK cell-mediated immunity toward malignant cells and viruses, there is a relative lack of data on the interplay between NK cells and filamentous fungi, especially Aspergillus fumigatus, which is the major cause of invasive aspergillosis. By studying the in vitro interaction between human NK cells and A. fumigatus, we found only germinated morphologies to be highly immunogenic, able to induce a Th1-like response, and capable of upregulating cytokines such as IFN-γ and TNF-α. Moreover, priming NK cells with human rIL-2 and stimulating NK cells by direct NK cell-pathogen contact were essential to induce damage against A. fumigatus. However, the most interesting finding was that NK cells did not mediate anti-Aspergillus cytotoxicity through degranulation of their cytotoxic proteins (perforin, granzymes, granulysine), but via an alternative mechanism involving soluble factor(s). To our knowledge, our study is the first to demonstrate that IFN-γ, released by NK cells, directly damages A. fumigatus, attributing new properties to both human NK cells and IFN-γ and suggesting them as possible therapeutic tools against IA.
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, 97080 Würzburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bouzani
authors.forename: Michael
authors.initials: M
authors.lastname: Ok
authors.forename: Allison
authors.initials: A
authors.lastname: McCormick
authors.forename: Frank
authors.initials: F
authors.lastname: Ebel
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Morton
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Juergen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000633:toxicity; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D013172:Spores, Fungal / Q000254:growth & development / Q000276:immunology
chemical_list: D000935:Antifungal Agents; D007371:Interferon-gamma