NK Cells Accumulate in Infected Tissues and Contribute to Pathogenicity of Ebola Virus in Mice
NK Cells Accumulate in Infected Tissues and Contribute to Pathogenicity of Ebola Virus in Mice
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DOI：
10.1128/jvi.01703-18
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发表时间：
2019-05-01
影响因子：
5.4
通讯作者：
Kobinger, G.
中科院分区：
文献类型：
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作者：
Fausther-Bovendo, H.;Qiu, X.;Kobinger, G.
了解埃博拉病毒(EBOV)感染后存活的免疫参数对于制定对策至关重要。在致命的EBOV感染中，循环和淋巴组织中的NK和T细胞水平在死亡前都会急剧下降。然而，这些淋巴细胞在病毒复制部位的命运仍然未知。本研究采用逆转录-聚合酶链式反应(RT-PCR)和荧光激活细胞分选(FACS)技术，检测了小鼠EBOV(MA-EBOV)感染后不同组织中淋巴细胞的频率。体循环中NK细胞数量的减少伴随着支持EBOV活跃复制的组织中这些细胞的增加。出乎意料的是，在特定条件下，病毒复制部位的NK积聚与EBOV疾病进展加速相关；在高激发剂量下，NK耗尽的小鼠表现出较低的病毒血症和肝脏损害，以及较高的肝脏T细胞水平。肝T细胞UL16结合蛋白-1(ULBP-1)表达上调，提示NK细胞参与其清除。总体而言，这项研究支持NK细胞在感染EBOV的组织中积累并可能导致病毒致病的概念。埃博拉病毒(EBOV)的爆发可以夺走无数人的生命，也会摧毁受影响国家的当地卫生基础设施和经济。致命的EBOV感染已被证明会降低血液中防御宿主所必需的几种免疫细胞的水平。然而，在EBOV感染后存活的人中，没有观察到免疫细胞的这种减少。因此，更好地掌握这些免疫细胞是如何丢失的，对于开发和改进新的和现有的治疗方法具有非常重要的意义。我们研究的意义在于确定致死性EBOV感染中免疫细胞明显丧失的机制。这将提供旨在防止这些免疫细胞损失的治疗选择，从而使感染者能够更好地抗击感染。
Understanding the immune parameters responsible for survival following Ebola virus (EBOV) infection is paramount for developing countermeasures. In lethal EBOV infections, levels of both NK and T cells decline drastically in the circulation and lymphoid tissues before death. However, the fate of these lymphocytes in viral replication sites remains unknown. In this study, reverse transcription-PCR (RT-PCR) and fluorescence-activated cell sorting (FACS) analysis were used to investigate lymphocyte frequencies in various infected mouse tissues after challenge with mouse-adapted EBOV (MA-EBOV). A decrease in NK cell numbers from systemic circulation was observed concomitant to an increase of these cells in tissues that are supporting active replication of EBOV. Unexpectedly, NK accumulation in virus replication sites correlated with enhanced EBOV disease progression in specific conditions; at a high challenge dose, NK-depleted mice displayed lower viremia and liver damage and higher hepatic T cell levels. Upregulation of UL16 binding protein 1 (ULBP-1) was detected in hepatic T cells, suggesting that NK cells participate in their elimination. Overall, this study supports the concept that NK cells accumulate in EBOV-infected tissues and can contribute to viral pathogenicity.IMPORTANCE Ebola virus (EBOV) outbreaks can claim numerous lives and also devastate the local health infrastructure, as well as the economy, of affected countries. Lethal EBOV infection has been documented to decrease the levels of several immune cells in the blood that are necessary to defend the host. This decrease in immune cells is, however, not observed in individuals who survive EBOV infection. Having a better grasp of how these immune cells are lost is therefore of high importance to develop and improve new and existing therapeutics. The significance of our research is in identifying the mechanism responsible for the apparent loss of immune cells in lethal EBOV infection. This will allow therapeutic options aimed at preventing the loss of these immune cells, therefore allowing infected individuals to better fight the infection.