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

J 2020

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

BENDÍČKOVÁ, Kamila, Federico TIDU, Marco DE ZUANI, Marcela HORTOVÁ KOHOUTKOVÁ, Ivana ANDREJČINOVÁ et. al.

Basic information

Original name

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

Authors

BENDÍČKOVÁ, Kamila (203 Czech Republic), Federico TIDU (380 Italy, belonging to the institution), Marco DE ZUANI (203 Czech Republic), Marcela HORTOVÁ KOHOUTKOVÁ (203 Czech Republic), Ivana ANDREJČINOVÁ (203 Czech Republic), Antonio POMPEIANO (203 Czech Republic), Silvie BĚLÁŠKOVÁ (203 Czech Republic), Giancarlo FORTE (203 Czech Republic), Teresa ZELANTE (380 Italy) and Jan FRIČ (203 Czech Republic, guarantor)

Edition

Journal of Leukocyte Biology, New York, Society for Leukocyte Biology, 2020, 0741-5400

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.962

RIV identification code

RIV/00216224:14110/20:00115426

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/JLB.4VMA0318-138R

UT WoS

000515440500012

Keywords in English

antifungal response; cyclosporine A; pattern recognition receptor signaling; Tacrolimus

Abstract

V originále

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.

Links

MUNI/A/0951/2019, interní kód MU

Name: Buněčná a molekulární biologie pro Biomedicínské vědy

Investor: Masaryk University, Category A

Citovat

BENDÍČKOVÁ, Kamila, Federico TIDU, Marco DE ZUANI, Marcela HORTOVÁ KOHOUTKOVÁ, Ivana ANDREJČINOVÁ, Antonio POMPEIANO, Silvie BĚLÁŠKOVÁ, Giancarlo FORTE, Teresa ZELANTE and Jan FRIČ. Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes. Journal of Leukocyte Biology. New York: Society for Leukocyte Biology, 2020, vol. 107, No 3, p. 497-508. ISSN 0741-5400. Available from: https://dx.doi.org/10.1002/JLB.4VMA0318-138R.

@article{1637457,
   author = {Bendíčková, Kamila and Tidu, Federico and De Zuani, Marco and Hortová Kohoutková, Marcela and Andrejčinová, Ivana and Pompeiano, Antonio and Bělášková, Silvie and Forte, Giancarlo and Zelante, Teresa and Frič, Jan},
   article_location = {New York},
   article_number = {3},
   doi = {http://dx.doi.org/10.1002/JLB.4VMA0318-138R},
   keywords = {antifungal response; cyclosporine A; pattern recognition receptor signaling; Tacrolimus},
   language = {eng},
   issn = {0741-5400},
   journal = {Journal of Leukocyte Biology},
   title = {Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes},
   url = {http://dx.doi.org/10.1002/JLB.4VMA0318-138R},
   volume = {107},
   year = {2020}
}

TY  - JOUR
ID  - 1637457
AU  - Bendíčková, Kamila - Tidu, Federico - De Zuani, Marco - Hortová Kohoutková, Marcela - Andrejčinová, Ivana - Pompeiano, Antonio - Bělášková, Silvie - Forte, Giancarlo - Zelante, Teresa - Frič, Jan
PY  - 2020
TI  - Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes
JF  - Journal of Leukocyte Biology
VL  - 107
IS  - 3
SP  - 497-508
EP  - 497-508
PB  - Society for Leukocyte Biology
SN  - 07415400
KW  - antifungal response
KW  - cyclosporine A
KW  - pattern recognition receptor signaling
KW  - Tacrolimus
UR  - http://dx.doi.org/10.1002/JLB.4VMA0318-138R
L2  - http://dx.doi.org/10.1002/JLB.4VMA0318-138R
N2  - 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.
ER  -

BENDÍČKOVÁ, Kamila, Federico TIDU, Marco DE ZUANI, Marcela HORTOVÁ KOHOUTKOVÁ, Ivana ANDREJČINOVÁ, Antonio POMPEIANO, Silvie BĚLÁŠKOVÁ, Giancarlo FORTE, Teresa ZELANTE and Jan FRIČ. Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes. \textit{Journal of Leukocyte Biology}. New York: Society for Leukocyte Biology, 2020, vol.~107, No~3, p.~497-508. ISSN~0741-5400. Available from: https://dx.doi.org/10.1002/JLB.4VMA0318-138R.

Detailed Information on Publication Record