Tnf-α expression and promoter sequences reflect the balance of tolerance/resistance to Puumala hantavirus infection in European bank vole populations
Tnf-α expression and promoter sequences reflect the balance of tolerance/resistance to Puumala hantavirus infection in European bank vole populations
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DOI：
10.1016/j.meegid.2010.07.022
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发表时间：
2010-12-01
影响因子：
3.2
通讯作者：
Charbonnel, Nathalie
中科院分区：
文献类型：
--
作者：
Guivier, Emmanuel;Galan, Maxime;Charbonnel, Nathalie
肿瘤坏死因子-α (TNF-α) 会影响限制寄生虫感染的能力，但其过量产生可能会导致炎症性疾病。因此，Tnf-α 基因表达水平可以介导对感染的耐受/抵抗的平衡。这项研究的重点是其啮齿动物宿主银行田鼠（Myodes glareolus）中的普马拉汉坦病毒（PUUV）感染。在人类中，PUUV 会导致轻微的肾综合征出血热、流行性肾病 (NE)。 NE 的严重程度与 TNF-α 的过量产生有关。相比之下，银行田鼠的 PUUV 感染是慢性且无症状的。 PUUV 与其宿主之间不同的共同进化历史可能会导致对 PUUV 感染的抵抗/耐受的不同平衡，至少部分是由 TNF-α 的不同产生水平介导的。我们研究了这样的假设：与来自 PUUV 流行地区的田鼠相比，来自 PUUV 流行地区的田鼠应表现出更高水平的耐受性，即较低水平的 TNF-α 产生。为此，我们分析了欧洲田鼠群体中 Tnf-α 基因表达和启动子序列的变异。我们的结果显示，PUUV 感染的田鼠中 Tnf-α 基因表达不存在上调，并且 Tnf-α 基因表达水平与 PUUV 流行性存在显着差异。这些结果证实了 PUUV 耐受/抗性不同平衡的假设。 Tnf-α启动子内的两个单核苷酸多态性基因型（-302 GG/GG和-296 A/A）与较高的Tnf-α基因表达相关，并且在非流行地区更常见。这项研究强调了选择对 TNF-α 产生的潜在影响，并调节银行田鼠对 PUUV 的耐受性/抗性平衡。进一步的研究，包括表型可塑性和寄生虫群落对 Tnf-α 表达水平的作用，应该为了解 PUUV 在欧洲的流行情况提供重要的关键。 (C) 2010 Elsevier B.V. 保留所有权利。
The tumor necrosis factor-alpha (TNF-alpha) influences the ability to limit parasite infection but its over-production might result in inflammatory disorders. The level of Tnf-alpha gene expression could thus mediate a balance of tolerance/resistance to infections. This study focused on Puumala hantavirus (PUUV) infection in its rodent host, the bank vole (Myodes glareolus). In humans, PUUV is responsible of a mild form of hemorrhagic fever with renal syndrome, nephropathia epidemica (NE). The severity of NE is associated with an over-production of TNF-alpha. By contrast, PUUV infection in bank vole is chronic and asymptomatic. It is likely that different coevolutionary histories between PUUV and its hosts could lead to different balances of resistance/tolerance to PUUV infection, at least partly mediated by variable production levels of TNF-alpha. We investigated the hypothesis that bank voles from PUUV endemic areas should exhibit higher levels of tolerance, i.e. lower levels of TNF-alpha production, than bank voles from areas where PUUV prevalence is low. For this purpose, we analysed variations of Tnf-alpha gene expression and promoter sequences among European populations of bank voles. Our results revealed an absence of up-regulation of Tnf-alpha gene expression in PUUV infected bank voles and significant differences in Tnf-alpha gene expression level with regard to PUUV endemicity. These results corroborated the hypothesis of different balances of tolerance/resistance to PUUV. Two single-nucleotide polymorphism genotypes within the Tnf-alpha promoter (-302 GG/GG and -296 A/A) were associated with higher Tnf-alpha gene expression and were more frequent in non-endemic areas. This study emphasized the potential influence of selection acting on TNF-alpha production and mediating a tolerance/resistance balance to PUUV in bank voles. Further investigations, including the role of phenotypic plasticity and parasite communities on Tnf-alpha expression levels, should provide important keys to understand the prevalence of PUUV over Europe. (C) 2010 Elsevier B.V. All rights reserved.