Neurons produce type I interferon during viral encephalitis
Neurons produce type I interferon during viral encephalitis
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DOI：
10.1073/pnas.0602460103
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发表时间：
2006-05-16
影响因子：
11.1
通讯作者：
Michiels, Thomas
中科院分区：
文献类型：
--
作者：
Delhaye, Sophie;Paul, Sophie;Michiels, Thomas
I 型干扰素，也称为 IFN-α/β，是抵御病毒感染的第一道防线。外周主要的 IFN-α/β 产生者是浆细胞样树突状细胞 (pDC)。 IFN 调节因子 (IRF)-7 的组成型表达使 pDC 能够在病毒感染后快速合成大量 IFN-α/β。在中枢神经系统 (CNS) 中，pDC 被认为不存在于实质中，并且人们对产生 IFN-α/β 的细胞知之甚少。本文介绍的研究旨在鉴定被嗜神经病毒（例如泰勒病毒和拉克罗斯病毒）感染后中枢神经系统体内产生 IFN-α/β 的细胞。在未感染小鼠的 CNS 中没有检测到 IRF-7 高组成型表达的细胞，表明不存在相当于 pDC 的细胞。病毒感染后，IFN-β 和 IFN-α 的某些亚型（但 IFN-ε 或 IFN-κ 除外）转录上调。 IFN-α/β 主要由分散的实质细胞产生，很少由炎症灶细胞产生。有趣的是，除了一些巨噬细胞和室管膜细胞外，神经元也是 IFN-α 和 IFN-β 的重要产生者。然而，只有 3% 的受感染神经元产生 IFN-α/β，这表明这些细胞中存在对 IFN-α/β 产生的一些限制。分析的所有 CNS 细胞类型（包括神经元）都能够通过产生 Mx 或 IRF-7 对 I 型 IFN 作出反应。我们的数据表明，在体内，神经元作为 IFN-α/β 的产生者和应答者，积极参与抗病毒防御。
Type I interferons, also referred to as IFN-alpha/beta, form the first line of defense against viral infections. Major IFN-alpha/beta producers in the periphery are the plasmacytoid dendritic cells (pDCs). Constitutive expression of the IFN regulatory factor (IRF)-7 enables pDCs to rapidly synthesize largea mounts of IFN-alpha/beta after viral infection. In the central nervous system (CNS), pDCs are considered to be absent from the parenchyma, and little is known about the cells producing IFN-alpha/beta. The study presented here aimed to identify the cells producing IFN-alpha/beta in the CNS in vivo after infection by neurotropic viruses such as Theiler's virus and La Crosse virus. No cells with high constitutive expression of IRF-7 were detected in the CNS of uninfected mice, suggesting the absence of cells equivalent to pDCs. Upon viral infection, IFN-beta and some subtypes of IFN-alpha, but not IFN-epsilon or IFN-kappa, were transcriptionally up-regulated. IFN-alpha/beta was predominantly produced by scattered parenchymal cells and much less by cells of inflammatory foci. Interestingly, in addition to some macrophages and ependymal cells, neurons turned out to be important producers of both IFN-alpha and IFN-beta. However, only 3% of the infected neurons produced IFN-alpha/beta, suggesting that some restriction to IFN-alpha/beta production existed in these cells. All CNS cell types analyzed, including neurons, were able to respond to type I IFN by producing Mx or IRF-7. Our data show that, in vivo, neurons take an active part to the antiviral defense by being both IFN-alpha/beta producers and responders.