Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells
| Autor: | Elisabeth Förster-Waldl, Lukas Wisgrill, Isabelle Wessely, Kambis Sadeghi, Antonia Netzl, Linda Pummer, Angelika Berger, Andreas Spittler |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Adolescent Interferon Regulatory Factor-7 Immunology Population Stimulation Biology Article neonatal Immunity 03 medical and health sciences 0302 clinical medicine Immune system Immunology and Allergy Humans Interleukin 29 STAT1 Receptor education Receptors Interferon Toll-like receptor education.field_of_study toll‐like receptor Interleukins Infant Newborn Interferon-alpha hemic and immune systems Cell Biology Dendritic Cells interleukin‐29 Host Defense & Pathophysiology Interleukin-10 030104 developmental biology STAT1 Transcription Factor Oligodeoxyribonucleotides plasmacytoid dendritic cells 030220 oncology & carcinogenesis Toll-Like Receptor 9 type III interferons biology.protein IRF7 Female Interferons |
| Zdroj: | Journal of Leukocyte Biology |
| ISSN: | 1938-3673 |
| Popis: | 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. Reduced IL‐29 secretion and responsiveness of neonatal plasmacytoid dendritic cells mainly contributes to reduced IFNα response against viral components. |
| Databáze: | OpenAIRE |
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