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

Eur J Immunol. 2008 Feb;38(2):507-17. 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-alpha 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-alpha/beta 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytomegalovirus / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Fetal Blood / cytology*
  • Fetal Blood / immunology*
  • Fetal Blood / virology
  • Herpesvirus 1, Human / immunology
  • Humans
  • Infant, Newborn
  • Interferon Regulatory Factor-7 / agonists
  • Interferon Regulatory Factor-7 / antagonists & inhibitors
  • Interferon Regulatory Factor-7 / deficiency*
  • Interferon Regulatory Factor-7 / physiology
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / deficiency
  • Interferon-alpha / metabolism
  • Interferon-beta / biosynthesis*
  • Interferon-beta / deficiency
  • Interferon-beta / metabolism
  • Ligands


  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Ligands
  • Interferon-beta