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Calcineurin inhibitors reduce NFAT‐dependent expression of antifungal pentraxin‐3 by human monocytes
Author(s) -
Bendíčková Kamila,
Tidu Federico,
De Zuani Marco,
Kohoutková Marcela Hortová,
Andrejčinová Ivana,
Pompeiano Antonio,
Bělášková Silvie,
Forte Giancarlo,
Zelante Teresa,
Frič Jan
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.4vma0318-138r
Subject(s) - nfat , calcineurin , biology , aspergillus fumigatus , monocyte , immune system , immunology , transcription factor , microbiology and biotechnology , gene , transplantation , biochemistry , medicine
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.