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Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes.

Authors
  • Bendíčková, Kamila1
  • Tidu, Federico1, 2
  • De Zuani, Marco1
  • Kohoutková, Marcela Hortová1
  • Andrejčinová, Ivana1
  • Pompeiano, Antonio1
  • Bělášková, Silvie1
  • Forte, Giancarlo1
  • Zelante, Teresa3
  • Frič, Jan1
  • 1 International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic. , (Czechia)
  • 2 Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. , (Czechia)
  • 3 Department of Experimental Medicine, University of Perugia, Perugia, Italy. , (Italy)
Type
Published Article
Journal
Journal of Leukocyte Biology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Mar 01, 2020
Volume
107
Issue
3
Pages
497–508
Identifiers
DOI: 10.1002/JLB.4VMA0318-138R
PMID: 30934147
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Calcineurin (CN) inhibitors are effective clinical immunosuppressants but leave patients vulnerable to potentially fatal fungal infections. This study tested the hypothesis that CN inhibition interferes with antifungal immune defenses mediated by monocytes. We showed that NFAT is expressed by human monocytes, and is activated by exposure to fungal ligands. We confirmed that NFAT translocation potently activated target gene transcription using a human monocytic reporter cell line. Inhibition of CN-NFAT by cyclosporine A significantly reduced monocyte production of TNF-α, IL-10, and MCP-1 proteins in response to pattern recognition receptor ligands as well as to Aspergillus fumigatus conidia. Moreover, we revealed that human monocytes express the antifungal protein pentraxin-3 under control of NFAT. In conclusion, clinical CN inhibitors have the potential to interfere with the novel NFAT-dependent pentraxin-3 pathway as well as antifungal cytokine production in human monocytes, thereby impeding monocyte-mediated defenses against fungal infection in immune-suppressed patients. © 2019 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology.

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