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 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.
Danis
Bénédicte
B
Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Charleroi, Belgium.
George
Thaddeus C
TC
Goriely
Stanislas
S
Dutta
Binita
B
Renneson
Joëlle
J
Gatto
Laurent
L
Fitzgerald-Bocarsly
Patricia
P
Marchant
Arnaud
A
Goldman
Michel
M
Willems
Fabienne
F
De Wit
Dominique
D
D000328:Adult; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D050839:Interferon Regulatory Factor-7 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000502:physiology; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D008024:Ligands
D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D008024:Ligands; D016899:Interferon-beta