Application of gene transformation technologies to the functional analysis of immunomodulation in Plasmodium

疟疾是最致命的人类寄生虫病，每年造成200多万人死亡。开发有效的抗疟疾疗法的努力受到了阻碍，因为人们不完全了解寄生虫是如何适应如此有效地增殖，同时又逃避免疫反应的。啮齿动物寄生虫沙巴蒂疟原虫（Plasmodium chabaudi）为解决这些问题提供了最好的实验模型，但到目前为止，由于缺乏针对这种寄生虫的基因修饰技术，因此无法对相关基因产物进行直接的功能研究。在最近的一项试点研究中，我们已经建立了chabaudi Plasmoduim基因改造的条件，并成功地产生了第一批荧光寄生虫。这些和其他寄生虫系将立即成为实验中的宝贵工具，这些实验将可视化寄生虫与宿主免疫细胞和组织之间的活体相互作用，并将在体内环境中检查宿主对特定寄生虫蛋白的反应。

Malaria is the most lethal human parasitic disease, causing more than 2 million deaths annually. Efforts to develop effective anti-malarial therapies have been hindered by an incomplete understanding of how parasites have adapted to proliferate so effectively whilst also evading immune responses. The rodent parasite, Plasmodium chabaudi, provides the best available experimental model for addressing these questions but, until now the lack of gene modification technologies for this parasite has precluded direct functional studies on the gene products that are implicated. In a recent pilot study we have established the conditions for Plasmoduim chabaudi genetic modification and have successfully generated the first fluorescent parasites. These and other parasite lines will immediately be an invaluable tool in experiments that will visualise live interactions between parasite and host immune cells and tissues and that will examine host responses to specific parasite proteins in an in vivo setting.