Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells
Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells
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DOI：
10.1189/jlb.0603255
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发表时间：
2003-12-01
影响因子：
5.5
通讯作者：
Fitzgerald-Bocarsly, P
中科院分区：
文献类型：
--
作者：
Izaguirre, A;Barnes, BJ;Fitzgerald-Bocarsly, P
浆细胞样树突状细胞 (PDC) 在病毒刺激后产生高水平的 I 型 IFN，而单核细胞和单核细胞衍生的树突状细胞 (MDDC) 产生的水平明显较低。为了找出 PDC 中 I 型 IFN 高产量的决定因素，我们检查了 IRF 转录因子的相对水平，其中一些转录因子在 IFN 的诱导中发挥着关键作用。此外，为了确定差异是否可能是由不同 IFNA 亚型的表达引起的，检查了表达的 IFNA 基因的概况。 PDC 通过产生高水平的 I 型 IFN，对 HSV-1 和仙台病毒 (SV) 的刺激反应同样良好，而 MDDC 和单核细胞对 SV 的反应较低，并且都不对 HSV-1 反应良好。所有三个群体均组成型表达大部分 IRF 基因。然而，实时 RT-PCR 表明，与单核细胞相比，PDC 中 IRF-7 转录物的水平有所增加。通过细胞内流式细胞术测定，PDC 组成型表达的 IRF-7 蛋白水平显着高于其他群体，而 IRF-3 水平在群体之间相似。对病毒刺激的 PDC、单核细胞和 MDDC 中表达的 IFNA 基因谱的分析表明，每个群体都表达 IFNA1 作为主要亚型，但 PDC 中表达的亚型范围更广泛，具有一些供体和刺激依赖性的变异性。我们得出的结论是，PDC（而非 MDDC）经过独特的预编程，可以快速有效地对一系列病毒病原体做出反应，由于高水平的组成型表达的 IRF-7，这些病原体会产生高水平的 IFN-α。
Plasmacytoid dendritic cells (PDC) produce high levels of type I IFN upon stimulation with viruses, while monocytes and monocyte-derived dendritic cells (MDDC) produce significantly lower levels. To find what determines the high production of type I IFN in PDC, we examined the relative levels of IRF transcription factors, some of which play critical roles in the induction of IFN. Furthermore, to determine whether the differences could result from expression of distinct IFNA subtypes, the profile of IFNA genes expressed was examined. PDC responded equally well to stimulation with HSV-1 and Sendai virus (SV) by producing high levels of type I IFN, whereas the MDDC and monocyte response to SV were lower, and neither responded well to HSV-1. All three populations constitutively expressed most of the IRF genes. However, real-time RT-PCR demonstrated increased levels of IRF-7 transcripts in PDC compared with monocytes. As determined by intracellular flow cytometry, the PDC constitutively expressed significantly higher levels of IRF-7 protein than the other populations while IRF-3 levels were similar among populations. Analysis of the profile of IFNA genes expressed in virus-stimulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes expressed in PDC was broader, with some donor and stimulus-dependent variability. We conclude that PDC but not MDDC are uniquely preprogrammed to respond rapidly and effectively to a range of viral pathogens with high levels of IFN-alpha production due to the high levels of constitutively expressed IRF-7.