title: Polymorphonuclear neutrophils and granulocytic myeloid-derived suppressor cells inhibit natural killer cell activity toward Aspergillus fumigatus.
abstract: Invasive aspergillosis is a devastating infectious disease in immunocompromised patients. Besides neutrophils and macrophages, natural killer (NK) cells have recently emerged as important players in immunity to this infection. It was shown that NK cells comprise an essential role in the clearance of Aspergillus fumigatus (A. fumigatus) in neutropenic but not in nonneutropenic mice. However, the antifungal activity of NK cells and their regulation have not been fully characterized. In this study, we investigated the interplay between polymorphonuclear neutrophils (PMNs) or granulocyte myeloid-derived suppressor cells (Gr-MDSCs) with NK cells. Both cell types exhibited an equal inhibitory effect on NK cell activation through downregulation of NKp30 expression on the cell surface and cytotoxicity towards the cell line K562. Furthermore, we showed that NK cell activation and antifungal cytotoxicity were impaired when NK cells had been cultured in the presence of PMNs or Gr-MDSCs before fungal stimulation. Besides the reduced cytotoxicity a decreased release of interferon gamma (IFNγ), a key player in the clearance of an A. fumigatus infection, was observed. Thus, inhibition of NK cell activity by PMNs or Gr-MDSCs might impair an effective anti-fungal immune response during recovery from conditions such as hematopoietic stem cell transplantation.
authors.affiliation: University Hospital Wuerzburg, Medical hospital II, WÜ4i, Wuerzburg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mueller-Leisse
authors.affiliation: University Hospital Wuerzburg, Medical hospital II, WÜ4i, Wuerzburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Brueggemann
authors.affiliation: University Hospital Wuerzburg, Medical hospital II, WÜ4i, Wuerzburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bouzani
authors.affiliation: University Hospital Wuerzburg, Medical hospital II, WÜ4i, Wuerzburg, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Schmitt
authors.affiliation: University Hospital Wuerzburg, Medical hospital II, WÜ4i, Wuerzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: University Hospital Wuerzburg, Medical hospital II, WÜ4i, Wuerzburg, Germany Loeffler_J@ukw.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006098:Granulocytes / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology*
chemical_list: D007371:Interferon-gamma
keywords: Aspergillus fumigatus; Interferon γ; granulocytic myeloid-derived suppressor cells; invasive aspergillosis; natural killer cells; polymorphonuclear neutrophils