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Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly,...

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Autores principales: Wisgrill, Lukas, Wessely, Isabelle, Netzl, Antonia, Pummer, Linda, Sadeghi, Kambis, Spittler, Andreas, Berger, Angelika, Förster‐Waldl, Elisabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852569/
https://www.ncbi.nlm.nih.gov/pubmed/31211458
http://dx.doi.org/10.1002/JLB.4A0518-189R
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author Wisgrill, Lukas
Wessely, Isabelle
Netzl, Antonia
Pummer, Linda
Sadeghi, Kambis
Spittler, Andreas
Berger, Angelika
Förster‐Waldl, Elisabeth
author_facet Wisgrill, Lukas
Wessely, Isabelle
Netzl, Antonia
Pummer, Linda
Sadeghi, Kambis
Spittler, Andreas
Berger, Angelika
Förster‐Waldl, Elisabeth
author_sort Wisgrill, Lukas
collection PubMed
description Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns.
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spelling pubmed-68525692019-11-21 Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells Wisgrill, Lukas Wessely, Isabelle Netzl, Antonia Pummer, Linda Sadeghi, Kambis Spittler, Andreas Berger, Angelika Förster‐Waldl, Elisabeth J Leukoc Biol Host Defense & Pathophysiology Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns. John Wiley and Sons Inc. 2019-06-18 2019-11 /pmc/articles/PMC6852569/ /pubmed/31211458 http://dx.doi.org/10.1002/JLB.4A0518-189R Text en © 2019 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Host Defense & Pathophysiology
Wisgrill, Lukas
Wessely, Isabelle
Netzl, Antonia
Pummer, Linda
Sadeghi, Kambis
Spittler, Andreas
Berger, Angelika
Förster‐Waldl, Elisabeth
Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells
title Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells
title_full Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells
title_fullStr Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells
title_full_unstemmed Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells
title_short Diminished secretion and function of IL‐29 is associated with impaired IFN‐α response of neonatal plasmacytoid dendritic cells
title_sort diminished secretion and function of il‐29 is associated with impaired ifn‐α response of neonatal plasmacytoid dendritic cells
topic Host Defense & Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852569/
https://www.ncbi.nlm.nih.gov/pubmed/31211458
http://dx.doi.org/10.1002/JLB.4A0518-189R
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