Abortively Infected Astrocytes Appear To Represent the Main Source of Interferon Beta in the Virus-Infected Brain
Abortively Infected Astrocytes Appear To Represent the Main Source of Interferon Beta in the Virus-Infected Brain
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DOI：
10.1128/jvi.02979-15
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发表时间：
2016-02-01
影响因子：
5.4
通讯作者：
Staeheli, Peter
中科院分区：
文献类型：
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作者：
Pfefferkorn, Cathleen;Kallfass, Carsten;Staeheli, Peter
干扰素β（IFN-β）是哺乳动物细胞先天免疫的关键组分，并且其构成病毒感染期间的第一道防线。以前对培养细胞的研究表明，几乎所有的有核细胞都能在不同程度上产生IFN-β，但有关IFN-β体内来源的信息仍然不完整。通过应用免疫组织化学和采用条件报告小鼠，表达萤火虫荧光素酶的控制下的IFN-β启动子在所有或只有不同的细胞类型，我们发现，星形胶质细胞是主要生产商的IFN-β感染后，大脑与各种嗜神经病毒，包括狂犬病病毒，泰勒的鼠脑脊髓炎病毒，水泡性口炎病毒。一组基因敲除小鼠品系的分析显示，通过RIG-I样解旋酶和Toll样受体检测病毒组分有助于在感染的大脑中诱导IFN。一种永久标记大脑中狂犬病病毒感染细胞的遗传方法表明，大量星形胶质细胞被标记，因此，必须至少暂时被病毒感染。因此，我们的研究结果强烈表明，星形胶质细胞的病毒感染失败可以触发模式识别受体信号传导事件，从而导致IFN-β的分泌，从而提供抗病毒保护。
Interferon beta (IFN-beta) is a key component of cellular innate immunity in mammals, and it constitutes the first line of defense during viral infection. Studies with cultured cells previously showed that almost all nucleated cells are able to produce IFN-beta to various extents, but information about the in vivo sources of IFN-beta remains incomplete. By applying immunohistochemistry and employing conditional-reporter mice that express firefly luciferase under the control of the IFN-beta promoter in either all or only distinct cell types, we found that astrocytes are the main producers of IFN-beta after infection of the brain with diverse neurotropic viruses, including rabies virus, Theiler's murine encephalomyelitis virus, and vesicular stomatitis virus. Analysis of a panel of knockout mouse strains revealed that sensing of viral components via both RIG-I-like helicases and Toll-like receptors contributes to IFN induction in the infected brain. A genetic approach to permanently mark rabies virus-infected cells in the brain showed that a substantial number of astrocytes became labeled and, therefore, must have been infected by the virus at least transiently. Thus, our results strongly indicate that abortive viral infection of astrocytes can trigger pattern recognition receptor signaling events which result in secretion of IFN-beta that confers antiviral protection.