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

• 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
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200737760

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.