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Open AccessArticle

Distinct Effects of Immunosuppressive Drugs on the Anti-Aspergillus Activity of Human Natural Killer Cells

1
Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Goethe University Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
2
Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
*
Author to whom correspondence should be addressed.
Pathogens 2019, 8(4), 246; https://doi.org/10.3390/pathogens8040246
Received: 7 October 2019 / Revised: 1 November 2019 / Accepted: 14 November 2019 / Published: 19 November 2019
(This article belongs to the Section Immunological Responses and Immune Defense Mechanisms)
As the prognosis of invasive aspergillosis remains unacceptably poor in patients undergoing hematopoietic stem cell transplantation (HSCT), there is a growing interest in the adoptive transfer of antifungal effector cells, such as Natural Killer (NK) cells. Because immunosuppressive agents are required in most HSCT recipients, knowledge of the impact of these compounds on the antifungal activity of NK cells is a prerequisite for clinical trials. We, therefore, assessed the effect of methylprednisolone (mPRED), cyclosporin A (CsA) and mycophenolic acid (MPA) at different concentrations on proliferation, apoptosis/necrosis, and the direct and indirect anti-Aspergillus activity of human NK cells. Methylprednisolone decreased proliferation and increased apoptosis of NK cells in a significant manner. After seven days, a reduction of viable NK cells was seen for all three immunosuppressants, which was significant for MPA only. Cyclosporin A significantly inhibited the direct hyphal damage by NK cells in a dose-dependent manner. None of the immunosuppressive compounds had a major impact on the measured levels of interferon-γ, granulocyte-macrophage colony-stimulating factor and RANTES (regulated on activation, normal T cell expressed and secreted; CCL5). Our data demonstrate that commonly used immunosuppressive compounds have distinct effects on proliferation, viability and antifungal activity of human NK cells, which should be considered in designing studies on the use of NK cells for adoptive antifungal immunotherapy. View Full-Text
Keywords: Aspergillus fumigatus; human Natural Killer cell; immunosuppressive drug; cyclosporin A; methylprednisolone; mycophenolic acid Aspergillus fumigatus; human Natural Killer cell; immunosuppressive drug; cyclosporin A; methylprednisolone; mycophenolic acid
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Schmidt, S.; Schubert, R.; Demir, A.; Lehrnbecher, T. Distinct Effects of Immunosuppressive Drugs on the Anti-Aspergillus Activity of Human Natural Killer Cells. Pathogens 2019, 8, 246.

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