Interferon regulatory factor 7-mediated responses are defective in cord blood plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDC) are specialized in massive production of type I interferons (IFN) upon viral infections. Activation of IFN regulatory factor (IRF)-7 is critically required for the synthesis of type I IFN in pDC. IRF-7 is highly expressed by resting pDC and translocates into the nu...

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Bibliographic Details
Published in:European journal of immunology 2008-02, Vol.38 (2), p.507-517
Main Authors: Danis, Bénédicte, George, Thaddeus C, Goriely, Stanislas, Dutta, Binita, Renneson, Joëlle, Gatto, Laurent, Fitzgerald-Bocarsly, Patricia, Marchant, Arnaud, Goldman, Michel, Willems, Fabienne, De Wit, Dominique
Format: Article
Language:English
Subjects:
Adult
Cells, Cultured
Cord blood
Cytomegalovirus - immunology
Dendritic cell
Dendritic Cells - immunology
Dendritic Cells - metabolism
Fetal Blood - cytology
Fetal Blood - immunology
Fetal Blood - virology
Herpesvirus 1, Human - immunology
Humans
IFN‐α
Infant, Newborn
Interferon Regulatory Factor-7 - agonists
Interferon Regulatory Factor-7 - antagonists & inhibitors
Interferon Regulatory Factor-7 - deficiency
Interferon Regulatory Factor-7 - physiology
Interferon regulatory factor 7
Interferon-alpha - biosynthesis
Interferon-alpha - deficiency
Interferon-alpha - metabolism
Interferon-beta - biosynthesis
Interferon-beta - deficiency
Interferon-beta - metabolism
Ligands
Newborn
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Summary:Plasmacytoid dendritic cells (pDC) are specialized in massive production of type I interferons (IFN) upon viral infections. Activation of IFN regulatory factor (IRF)-7 is critically required for the synthesis of type I IFN in pDC. IRF-7 is highly expressed by resting pDC and translocates into the nucleus to initiate type I IFN transcription. In a previous work, we observed an impaired IFN-α production in enriched cord blood pDC following a TLR9 stimulation using CpG oligonucleotides. Herein, we show that highly purified pDC from cord blood exhibit a profound defect in their capacity to produce IFN-α/β in response to TLR9 as well as to TLR7 ligation or human CMV or HSV-1 exposure. Microarray experiments indicate that expression of the majority of type I IFN subtypes induced by a TLR7 agonist is reduced in cord blood pDC. We next demonstrated a reduced nuclear translocation of IRF-7 in cord blood pDC following CpG and HSV stimulation as compared to adult pDC. We conclude that impaired IRF-7 translocation in cord blood pDC is associated with defective expression of type I IFN genes. Our data provide a molecular understanding for the decreased ability of cord blood pDC to produce type I IFN upon viral stimulation.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200737760