Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns
Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns
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DOI：
10.1182/blood-2003-04-1216
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发表时间：
2004-02-01
期刊：
影响因子：
20.3
通讯作者：
Willems, F
中科院分区：
文献类型：
--
作者：
De Wit, D;Olislagers, V;Willems, F
浆细胞样树突状细胞（pDC）对存在于细菌DNA中的未甲基化胞嘧啶-磷酸-鸟苷（CpG）基序或未甲基化的合成寡脱氧核苷酸（CpG）应答。为了评估pDC在人类新生儿中的功能，在脐带血和成人血液中比较由CpG 2216诱导的干扰素-α（IFN-α）产生和响应于CpG 2006的pDC的表型成熟。我们首先观察到，新生儿pDC显示CD 80、CD 83、CD 86和CD 40的上调减少，而HLA-DR和CD 54的上调在成人和新生儿之间没有显著差异。然后我们发现，在脐带血中，响应于CpG的IFN-α的产生显著受损。这种新生儿缺陷在蛋白质和mRNA水平上都被检测到，并且仍然存在于4天大婴儿的血液中。对富集的pDC的进一步实验证实，这些细胞在出生时本质上缺乏CpG诱导的IFN-α产生。这些发现可能与人类新生儿对感染的易感性增加以及在新生儿期使用CpG寡脱氧核苷酸作为疫苗佐剂有关。
Plasmacytoid dendritic cells (pDCs) respond to unmethylated cytosine-phosphate-guanosine (CpG) motifs present in bacterial DNA or unmethylated synthetic oligodeoxynucleotides (CpG). In order to assess the function of pDCs in human newborns, interferon-alpha (IFN-alpha) production induced by CpG 2216 and phenotypic maturation of pDCs in response to CpG 2006 were compared in cord blood and adult blood. We first observed that neonatal pDCs displayed decreased up-regulation of CD80, CD83, CD86, and CD40, whereas HLA-DR and CD54 up-regulation did not differ significantly between adults and neonates. We then found that the production of IFN-alpha in response to CpG was dramatically impaired in cord blood. This neonatal defect was detected both at protein and mRNA levels and was still present in blood of 4-day-old babies. Further experiments on enriched pDCs confirmed that these cells are intrinsically deficient in CpG-induced IFN-alpha production at birth. These findings might be relevant to the increased susceptibility of human newborns to infections as well as to the use of CpG oligodeoxynucleotides as vaccine adjuvants in the neonatal period.