Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis

Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis
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DOI:
10.4049/jimmunol.0803798
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发表时间:
2009-05-15
影响因子:
4.4
通讯作者:
Koyasu, Shigeo
Koyasu, Shigeo
中科院分区:
医学2区
文献类型:
--
作者:
Hayashi, Toshiyuki;Nagai, Shigenori;Koyasu, Shigeo

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单核细胞增多性李斯特菌(Lm)是一种威胁生命的传染病,影响人类和家畜的大脑。不幸的是,目前还没有合适的中枢神经系统李斯特菌病小鼠模型。通过脑实质内注射,我们建立了一种新的中枢神经系统李斯特菌病小鼠模型。注射少量细菌悬浮液将细菌限制在脑实质,不会渗入脑室系统。这一新方法使我们能够研究李斯特菌脑感染的进展和康复,揭示了先天免疫细胞和获得性免疫细胞在中枢神经系统李斯特菌病中的作用。在中枢神经系统李斯特菌病的早期阶段,墨细胞来源的干扰素-γ是一种关键的细胞因子,通过宿主防御限制细菌的生长。在后期,CD8(+)T细胞发挥关键作用,而不是CD4(+)T细胞,而LM特异性CD8(+)T细胞杀死感染LM的小胶质细胞。因此,先天免疫反应和获得性免疫反应相结合,成功地清除了大脑中的细菌。免疫学杂志,2009,182:6360-6368。
Listeria monocytogenes (LM) causes a life-threatening infectious disease affecting the brain of humans and domestic animals. Unfortunately, no adequate murine models for CNS listeriosis exist. Using intraparenchymal injection, we have established a new murine model for CNS listeriosis. Injection of a small volume of bacterial suspension limits the bacteria to the brain parenchyma with no leakage into the ventricular system. This new method enabled us to investigate the progression of and recovery from listerial brain infection, revealing roles for both innate and adaptive immune cells in CNS listeriosis. In the early phase of CNS listeriosis, INK cell-derived IFN-gamma is a critical cytokine in the limitation of bacterial growth by the host defense. During the later phase, CD8(+) but not CD4(+) T cells play a critical role and LM-specific CD8(+) T cells kill LM-infected microglia. Thus, innate and adaptive immune responses combine to successfully eliminate bacteria from the brain. The Journal of Immunology, 2009, 182: 6360-6368.