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.
Affiliations
Université Libre de Bruxelles
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Chicago
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Danis, B., George, T. C., Goriely, S., Dutta, B., Renneson, J., Gatto, L., Fitzgerald-Bocarsly, P., Marchant, A., Goldman, M., Willems, F., & de Wit, D. (2008). Interferon regulatory factor 7-mediated responses are defective in cord blood plasmacytoid dendritic cells. European Journal of Immunology, 38(2), 507-517. https://doi.org/10.1002/eji.200737760 (Original work published 2008)