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IFN‐α production by cord blood plasmacytoid dendritic cells is totally deficient.
Author(s) -
Charrier Emily,
Dardari R’Kia,
Cordeiro Paulo,
Michaud Annie,
Duval Michel
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.44
Subject(s) - cord blood , biology , immunology , cd80 , tlr9 , immune system , plasmacytoid dendritic cell , interferon , cd40 , interleukin 12 , cytotoxic t cell , dendritic cell , in vitro , gene expression , biochemistry , dna methylation , gene
The interaction between natural killer cells (NK) and plasmacytoid dendritic cells (pDC) has been suggested to play a role during the early phase of the immune response to viral infections and tumors. NK cells can lyse tumor and virus‐infected cells and their cytolytic activity has long been known to be enhanced by interferon‐alpha (IFN‐α). Human pDC are a major source of IFN‐α following viral stimulation or upon exposure to TLR‐7 or TLR‐9 ligands. Objective: In order to study the cross‐talk between NK and pDC in human newborns, the effect of IFN‐α on NK cells was compared between cord and adult blood, and the response of pDC to CpG or HSV‐1 was studied. Results: We have recently reported that neonatal NK cells are mature and express a reduced cytolytic activity. In this study, we show that IFN‐α‐stimulated‐NK cells display an activated phenotype and a cytolytic activity similar to adult NK cells. Moreover, the production of IFN‐α in response to CpG or HSV‐1 is dramatically impaired in cord blood. Cord blood pDC present a decreased expression of TLR9 and IRF7 which may explain the deficient production of IFN‐α. This lower expression of IRF7 and IFN‐α production can be partially restored by pre‐treatment of IFN‐β. However, although all cord blood show a deficiency in IFN‐α production, most of cord blood samples (2/3) exhibit a normal maturation of pDC in response to CpG, as shown by the up‐regulation of CD80, CD83, CD40, HLA‐DR and CD54. Conclusions: The defect in IFN‐α production by cord blood plasmacytoid dendritic cells can be explained by the low level of IRF7 and TLR9 expression. This defect can be partially restored by increasing IRF7 expression by pre‐treatment of IFN‐β. These findings might explain the increased susceptibility of human newborns to infections.