Genetic manipulation of African trypanosomes as a tool to dissect the immunobiology of infection.
Genetic manipulation of African trypanosomes as a tool to dissect the immunobiology of infection.
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非洲锥虫的基因操作作为剖析感染免疫生物学的工具。
DOI：
10.1111/j.1365-3024.2007.01003.x
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发表时间：
2008
影响因子：
2.2
通讯作者：
Paulnock,DM
中科院分区：
文献类型：
--
作者：
Mansfield,JM;Paulnock,DM
非洲锥虫的变异表面糖蛋白（VSG）外壳表现出不同于其作为变异表面抗原的突出作用的免疫生物学功能。为了解决有关VSG开关变外壳的免疫隐身作用和脱落VSG取代基的先天免疫系统激活作用的问题，几个研究小组对锥虫在感染哺乳动物宿主期间表达或释放VSG的能力进行了基因改造。通过在表达内源性VSG基因的锥虫体内稳定共表达外源性VSG基因，以及敲除从膜中释放VSG的GPI磷脂酶C （PLC）的遗传位点，分别揭示了VSG开关变异体（VSG双表达体）表达的镶嵌表面外壳在逃避早期免疫检测中的作用，以及VSG糖基磷脂酰肌醇（GPI）锚定取代基在调节宿主免疫中的作用。非洲锥虫遗传修饰的两种方法都提出了与表面涂层分子相关的有趣和意想不到的免疫生物学效应。
The variant surface glycoprotein (VSG) coat of African trypanosomes exhibits immunobiological functions distinct from its prominent role as a variant surface antigen. In order to address questions regarding immune stealth effects of VSG switch‐variant coats, and the innate immune system activating effects of shed VSG substituents, several groups have genetically modified the ability of trypanosomes to express or release VSG during infection of the mammalian host. The role of mosaic surface coats expressed by VSG switch‐variants (VSG double‐expressors) in escaping early immune detection, and the role of VSG glycosylphosphatidylinositol (GPI) anchor substituents in regulating host immunity have been revealed, respectively, by stable co‐expression of an exogenous VSG gene in trypanosomes expressing an endogenous VSG gene, and by knocking out the genetic locus for GPI‐phospholipase C (PLC) that releases VSG from the membrane. Both approaches to genetic modification of African trypanosomes have suggested interesting and unexpected immunobiological effects associated with surface coat molecules.