Informace o publikaci

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

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BENDÍČKOVÁ Kamila TIDU Federico DE ZUANI Marco HORTOVÁ KOHOUTKOVÁ Marcela ANDREJČINOVÁ Ivana POMPEIANO Antonio BĚLÁŠKOVÁ Silvie FORTE Giancarlo ZELANTE Teresa FRIČ Jan

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Leukocyte Biology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.1002/JLB.4VMA0318-138R
Doi http://dx.doi.org/10.1002/JLB.4VMA0318-138R
Klíčová slova antifungal response; cyclosporine A; pattern recognition receptor signaling; Tacrolimus
Popis 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-alpha, 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.