par 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
Référence European Journal of Immunology, 38, 2, page (507-517)
Publication Publié, 2008-02
;George, Thaddeus C;Goriely, Stanislas ;Dutta, BINITA ;Renneson, Joëlle ;Gatto, Laurent ;Fitzgerald-Bocarsly, Patricia;Marchant, Arnaud ;Goldman, Michel ;Willems, Fabienne ;De Wit, Dominique Référence European Journal of Immunology, 38, 2, page (507-517)
Publication Publié, 2008-02
Article révisé par les pairs
| Résumé : | 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. |
