Antiviral-activated dendritic cells: a paracrine-induced response state.
Antiviral-activated dendritic cells: a paracrine-induced response state.
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DOI：
10.4049/jimmunol.181.10.6872
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发表时间：
2008-11-15
期刊：
影响因子：
--
通讯作者：
Sealfon SC
中科院分区：
文献类型：
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作者：
Bordería AV;Hartmann BM;Fernandez-Sesma A;Moran TM;Sealfon SC
未成熟树突状细胞（DC）被病毒感染后可刺激其成熟为抗原提呈细胞（APC）。感染的DC还可以通过旁分泌信号传导将未感染的DC暴露于一系列细胞因子/趋化因子。数学模型表明，高比率的旁分泌信号很可能发生在位于三维空间中的DC之间。关于分泌因子如何改变对病毒感染的早期反应，我们知之甚少。我们使用了一个trans-well实验系统，该系统允许分泌因子通过，但不直接接触，病毒感染的DC和未感染的DC之间，以调查旁分泌信号应答。来自受感染DC的旁分泌信号传导诱导了与成熟病毒感染DC不同的抗病毒致敏DC状态，我们将其称为抗病毒活化DC（AVDC）。AVDC表面MHC-II和CD 86水平增加，但与病毒感染的DC相反，它们的MHC-I水平没有变化。流式细胞仪成像显示AVDC的吞噬率比幼稚DC增加。IFNβ细胞因子的实验表明，它可能负责CD 86，而不是MHC-Ⅱ的调节，在AVDC。干扰素诱导型和干扰素非依赖型基因在AVDC中均上调。值得注意的是，与幼稚DC相比，AVDC对病毒感染具有相对抗性，并且在病毒感染的情况下实现了共刺激分子表达的加速和增强水平。AVDCs显示出由DC旁分泌信号介导的DC成熟的独特抗病毒引发状态。虽然需要进一步的体内研究，但AVDC的特性表明它非常适合在免疫系统的早期先天适应性转变中发挥作用。
Infection of immature dendritic cells (DCs) by virus stimulates their maturation into antigen presenting cells (APC). Infected DCs can also expose uninfected DCs to a panoply of cytokines/chemokines via paracrine signaling. Mathematical modeling suggests that a high rate of paracrine signaling is likely to occur among DCs located in three-dimensional space. Relatively little is known about how secreted factors modify the early response to virus infection. We used a trans-well experimental system that allows passage of secreted factors, but not direct contact, between virus-infected DCs and uninfected DCs to investigate paracrine signaling responses. Paracrine signaling from infected DCs induced an antiviral-primed DC state distinct from that of mature virus-infected DCs that we refer to as antiviral activated DCs (AVDCs). AVDCs had increased surface MHC-II and CD86 levels, but in contrast to virus-infected DCs, their MHC-I levels were unchanged. Imaging flow-cytometry showed that AVDCs had an increased rate of phagocytosis compared with naïve DCs. Experiments with IFNβ cytokine indicated that it may be responsible for CD86, but not MHC-II regulation, in AVDCs. Both interferon-inducible and interferon-independent genes are up-regulated in AVDCs. Notably, AVDCs are relatively resistant to virus infection in comparison with naïve DCs and achieve accelerated and augmented levels of co-stimulatory molecule expression with virus infection. AVDCs show a distinct antiviral-primed state of DC maturation mediated by DC paracrine signaling. While further in vivo study is needed, the characteristics of the AVDC suggest that it is well-suited to play a role in the early innate-adaptive transition of the immune system.