Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways

Abstract Treatment of patients with glucocorticoids can result in an increased risk of infection with pathogens such as fungi. Dectin-1 is a member of the C-type lectin receptor superfamily and was shown to be one of the major receptors for fungal beta-glucans. Activation of Dectin-1 increases the p...

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Autores principales:	Philipp Kotthoff, Annkristin Heine, Stefanie Andrea Erika Held, Peter Brossart
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b9c11a8f1ab472d8faa882f5dc2180c
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spelling	oai:doaj.org-article:3b9c11a8f1ab472d8faa882f5dc2180c2021-12-02T11:40:32ZDexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways10.1038/s41598-017-04558-z2045-2322https://doaj.org/article/3b9c11a8f1ab472d8faa882f5dc2180c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04558-zhttps://doaj.org/toc/2045-2322Abstract Treatment of patients with glucocorticoids can result in an increased risk of infection with pathogens such as fungi. Dectin-1 is a member of the C-type lectin receptor superfamily and was shown to be one of the major receptors for fungal beta-glucans. Activation of Dectin-1 increases the production of cytokines and chemokines and T-cell stimulatory capacity of DC and mediates resolution of fungal infections. Here we show that antigen-presenting cells generated in the presence of dexamethasone (Dex-DC) have a reduced capacity to stimulate T-cell proliferation and decreased expression of costimulatory molecules, that can not be enhanced upon stimulation with Dectin-1 ligands. Stimulation of Dex-DC with beta-glucans induced a strong upregulation of Syk phosphorylation and increased secretion of IL-10, while the production of IL-12, IL-23 and TNF-alpha was reduced. Downstream of Syk stimulation of Dectin-1 on Dex-DC resulted in phosphorylation of STAT3 and reduced nuclear localization of transcription factors involved in DC activation and function.Philipp KotthoffAnnkristin HeineStefanie Andrea Erika HeldPeter BrossartNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philipp Kotthoff Annkristin Heine Stefanie Andrea Erika Held Peter Brossart Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways
description	Abstract Treatment of patients with glucocorticoids can result in an increased risk of infection with pathogens such as fungi. Dectin-1 is a member of the C-type lectin receptor superfamily and was shown to be one of the major receptors for fungal beta-glucans. Activation of Dectin-1 increases the production of cytokines and chemokines and T-cell stimulatory capacity of DC and mediates resolution of fungal infections. Here we show that antigen-presenting cells generated in the presence of dexamethasone (Dex-DC) have a reduced capacity to stimulate T-cell proliferation and decreased expression of costimulatory molecules, that can not be enhanced upon stimulation with Dectin-1 ligands. Stimulation of Dex-DC with beta-glucans induced a strong upregulation of Syk phosphorylation and increased secretion of IL-10, while the production of IL-12, IL-23 and TNF-alpha was reduced. Downstream of Syk stimulation of Dectin-1 on Dex-DC resulted in phosphorylation of STAT3 and reduced nuclear localization of transcription factors involved in DC activation and function.
format	article
author	Philipp Kotthoff Annkristin Heine Stefanie Andrea Erika Held Peter Brossart
author_facet	Philipp Kotthoff Annkristin Heine Stefanie Andrea Erika Held Peter Brossart
author_sort	Philipp Kotthoff
title	Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways
title_short	Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways
title_full	Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways
title_fullStr	Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways
title_full_unstemmed	Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways
title_sort	dexamethasone induced inhibition of dectin-1 activation of antigen presenting cells is mediated via stat-3 and nf-κb signaling pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b9c11a8f1ab472d8faa882f5dc2180c
work_keys_str_mv	AT philippkotthoff dexamethasoneinducedinhibitionofdectin1activationofantigenpresentingcellsismediatedviastat3andnfkbsignalingpathways AT annkristinheine dexamethasoneinducedinhibitionofdectin1activationofantigenpresentingcellsismediatedviastat3andnfkbsignalingpathways AT stefanieandreaerikaheld dexamethasoneinducedinhibitionofdectin1activationofantigenpresentingcellsismediatedviastat3andnfkbsignalingpathways AT peterbrossart dexamethasoneinducedinhibitionofdectin1activationofantigenpresentingcellsismediatedviastat3andnfkbsignalingpathways
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Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways

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