Emerging challenges in understanding trypanosome antigenic variation.
Emerging challenges in understanding trypanosome antigenic variation.
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DOI：
10.1042/etls20170104
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发表时间：
2017-12-22
影响因子：
3.8
通讯作者：
Matthews K
中科院分区：
文献类型：
--
作者：
McCulloch R;Cobbold CA;Figueiredo L;Jackson A;Morrison LJ;Mugnier MR;Papavasiliou N;Schnaufer A;Matthews K
许多病原体通过周期性地改变其表面表达的蛋白质来逃避宿主免疫，这种现象被称为抗原变异。引起人类疾病的非洲布鲁氏锥虫表现出一种极端形式的抗原变异，其基础是改变变异表面糖蛋白（VSG）外壳的组成。在过去的三十年中，人们对布鲁氏t细胞中VSG转换的分子细节进行了广泛的研究，越来越详细地揭示了VSG表达被控制和改变的机制和机制。然而，已经出现的布鲁氏杆菌抗原变异模型的几个关键组成部分已经受到最近发现的挑战。这些发现包括对基因嵌合在产生大量新的VSG变异中的重要性的新的认识，寄生虫发育和宿主体内的体区隔对感染动力学的贡献，最后，关键的家畜锥虫刚果锥虫和间日锥虫所使用的抗原变异和宿主感染策略的潜在差异。这篇综述将讨论所有这些观察结果，这些观察结果对现有的锥虫抗原变异模型的安全性提出了疑问。此外，我们将讨论持续数学建模的重要性，以了解这种广泛的免疫生存过程的目的。
Many pathogens evade host immunity by periodically changing the proteins they express on their surface — a phenomenon termed antigenic variation. An extreme form of antigenic variation, based around switching the composition of a variant surface glycoprotein (VSG) coat, is exhibited by the African trypanosome Trypanosoma brucei, which causes human disease. The molecular details of VSG switching in T. brucei have been extensively studied over the last three decades, revealing in increasing detail the machinery and mechanisms by which VSG expression is controlled and altered. However, several key components of the models of T. brucei antigenic variation that have emerged have been challenged through recent discoveries. These discoveries include new appreciation of the importance of gene mosaics in generating huge levels of new VSG variants, the contributions of parasite development and body compartmentation in the host to the infection dynamics and, finally, potential differences in the strategies of antigenic variation and host infection used by the crucial livestock trypanosomes T. congolense and T. vivax. This review will discuss all these observations, which raise questions regarding how secure the existing models of trypanosome antigenic variation are. In addition, we will discuss the importance of continued mathematical modelling to understand the purpose of this widespread immune survival process.