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Impact of Antifungal Compounds on Viability and Anti-Aspergillus Activity of Human Natural Killer Cells.

Authors
  • Schmidt, Stanislaw1
  • Schubert, Ralf2
  • Tramsen, Lars1
  • Lehrnbecher, Thomas3
  • 1 Division of Pediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, Germany. , (Germany)
  • 2 Division of Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany. , (Germany)
  • 3 Division of Pediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, Germany [email protected] , (Germany)
Type
Published Article
Journal
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Publication Date
Feb 01, 2019
Volume
63
Issue
2
Identifiers
DOI: 10.1128/AAC.01993-18
PMID: 30455240
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Despite the availability of new antifungal compounds, invasive aspergillosis carries high morbidity and mortality in hematopoietic stem cell transplant recipients. In vitro studies and animal models suggest that the adoptive transfer of natural killer (NK) cells might be a promising immunotherapeutic option in this setting. As it is unclear whether the viability and function of human NK cells are affected by common antifungal agents, we analyzed the interaction of various concentrations of amphotericin B deoxycholate (AmB-D), liposomal amphotericin B, caspofungin, fluconazole, voriconazole, and posaconazole with human NK cells. When adding NK cells to therapeutic concentrations of antifungal agents, a significant increase in the antifungal effect was seen for caspofungin and voriconazole, whereas NK cells significantly decreased the hyphal damage of escalated doses of AmB-D. In contrast, therapeutic concentrations of all antifungal compounds tested did not have a negative effect on proliferation, viability, and the release of soluble immunomodulatory molecules of NK cells. These data indicate that therapeutic concentrations of the antifungal agents tested do not negatively affect the functional properties of human NK cells, which is a prerequisite for further studies evaluating NK cells as antifungal immunotherapy in immunocompromised patients suffering from invasive aspergillosis. Copyright © 2019 American Society for Microbiology.

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