Distinct effects of immunosuppressive drugs on the anti-aspergillus activity of human natural killer cells

  • 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.

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Author:Stanislaw Schmidt, Ralf SchubertORCiDGND, Asuman Demir, Thomas LehrnbecherORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31752374
Parent Title (English):Pathogens
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/11/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/01/13
Tag:Aspergillus fumigatus; cyclosporin A; human Natural Killer cell; immunosuppressive drug; methylprednisolone; mycophenolic acid
Issue:4, Art. 246
Page Number:12
First Page:1
Last Page:12
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0