Calcineurin-NFAT signaling controls neutrophils' ability of
chemoattraction upon fungal infection

J 2024

Calcineurin-NFAT signaling controls neutrophils' ability of chemoattraction upon fungal infection

VYMAZAL, Ondřej; Ioanna PAPATHEODOROU; Ivana ANDREJČINOVÁ; Veronika BOSÁKOVÁ; G. VASCELLI et al.

Základní údaje

Originální název

Calcineurin-NFAT signaling controls neutrophils' ability of chemoattraction upon fungal infection

Autoři

VYMAZAL, Ondřej; Ioanna PAPATHEODOROU; Ivana ANDREJČINOVÁ; Veronika BOSÁKOVÁ; G. VASCELLI; Kamila BENDÍČKOVÁ; T. ZELANTE; Marcela HORTOVÁ KOHOUTKOVÁ a Jan FRIČ

Vydání

Journal of Leukocyte Biology, OXFORD, OXFORD UNIV PRESS, 2024, 0741-5400

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.100

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/24:00139184

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

aspergillus; candida; chemokines; neutrophils; NFAT

Štítky

14110132, 14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 3. 2025 10:31, Mgr. Tereza Miškechová

Anotace

V originále

Calcineurin-nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor-treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus, in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2, CCL3, and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils.

Návaznosti

LM2018132, projekt VaV

Název: Národní centrum lékařské genomiky (Akronym: NCLG)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní centrum lékařské genomiky

LM2023067, projekt VaV

Název: Národní centrum lékařské genomiky

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, NCLG: Národní centrum lékařské genomiky

NU21-06-00408, projekt VaV

Název: Prediktivní potenciál dynamických změn v subpopulacích neutrofilů a monocytů ve vývoji SIRS a sepse po operaci nebo traumatu.

Investor: Ministerstvo zdravotnictví ČR, Prediktivní potenciál dynamických změn v subpopulacích neutrofilů a monocytů ve vývoji SIRS a sepse po operaci nebo traumatu., Podprogram 1 - standardní

Citovat

VYMAZAL, Ondřej; Ioanna PAPATHEODOROU; Ivana ANDREJČINOVÁ; Veronika BOSÁKOVÁ; G. VASCELLI; Kamila BENDÍČKOVÁ; T. ZELANTE; Marcela HORTOVÁ KOHOUTKOVÁ a Jan FRIČ. Calcineurin-NFAT signaling controls neutrophils' ability of chemoattraction upon fungal infection. Journal of Leukocyte Biology. OXFORD: OXFORD UNIV PRESS, 2024, roč. 116, č. 4, s. 816-829. ISSN 0741-5400. Dostupné z: https://doi.org/10.1093/jleuko/qiae091.

@article{2487005,
   author = {Vymazal, Ondřej and Papatheodorou, Ioanna and Andrejčinová, Ivana and Bosáková, Veronika and Vascelli, G. and Bendíčková, Kamila and Zelante, T. and Hortová Kohoutková, Marcela and Frič, Jan},
   article_location = {OXFORD},
   article_number = {4},
   doi = {https://doi.org/10.1093/jleuko/qiae091},
   keywords = {aspergillus; candida; chemokines; neutrophils; NFAT},
   language = {eng},
   issn = {0741-5400},
   journal = {Journal of Leukocyte Biology},
   title = {Calcineurin-NFAT signaling controls neutrophils' ability of chemoattraction upon fungal infection},
   url = {https://academic.oup.com/jleukbio/article/116/4/816/7656007?login=true},
   volume = {116},
   year = {2024}
}

TY  - JOUR
ID  - 2487005
AU  - Vymazal, Ondřej - Papatheodorou, Ioanna - Andrejčinová, Ivana - Bosáková, Veronika - Vascelli, G. - Bendíčková, Kamila - Zelante, T. - Hortová Kohoutková, Marcela - Frič, Jan
PY  - 2024
TI  - Calcineurin-NFAT signaling controls neutrophils' ability of chemoattraction upon fungal infection
JF  - Journal of Leukocyte Biology
VL  - 116
IS  - 4
SP  - 816-829
EP  - 816-829
PB  - OXFORD UNIV PRESS
SN  - 07415400
KW  - aspergillus
KW  - candida
KW  - chemokines
KW  - neutrophils
KW  - NFAT
UR  - https://academic.oup.com/jleukbio/article/116/4/816/7656007?login=true
N2  - Calcineurin-nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor-treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus, in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2, CCL3, and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils.
ER  -

VYMAZAL, Ondřej; Ioanna PAPATHEODOROU; Ivana ANDREJČINOVÁ; Veronika BOSÁKOVÁ; G. VASCELLI; Kamila BENDÍČKOVÁ; T. ZELANTE; Marcela HORTOVÁ KOHOUTKOVÁ a Jan FRIČ. Calcineurin-NFAT signaling controls neutrophils' ability of chemoattraction upon fungal infection. \textit{Journal of Leukocyte Biology}. OXFORD: OXFORD UNIV PRESS, 2024, roč.~116, č.~4, s.~816-829. ISSN~0741-5400. Dostupné z: https://doi.org/10.1093/jleuko/qiae091.

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