Antibody clearance as virulance factor in African sleeping sickness

人类非洲锥虫病，俗称昏睡病，是世界上最被忽视的传染病之一。锥虫通过采采蝇传播，不仅引起致命的人类感染，而且引起可怕的Nagana，这是一种具有戏剧性经济后果的兽医疾病。锥虫病是一种典型的贫困疾病。非洲锥虫是单细胞的鞭毛虫寄生虫，在哺乳动物的血液中茁壮成长。进化为血液寄生虫提供了独特的细胞表面涂层，由单一类型的变异表面糖蛋白（VSG）组成。我们发现，在培养中，宿主来源的抗体迅速从VSG外套中去除。定向细胞运动和质膜再循环的协调作用是清除宿主抗体的必要和充分条件，本项目的目标是探索自然锥虫感染过程中作为毒力因子的抗体清除，并利用所获得的知识开发新的治疗方法。我们制定了一项工作计划，要求非洲和德国伙伴密切合作。试验性办法利用了内罗毕和达姆施塔特的独特专门知识和资源。先进的分子细胞生物学和感染遗传学与活体动物实验，流行病学和生物信息学相结合。显然，我们项目的设计为参与其中的年轻科学家带来了独特的挑战和好处。

Human African trypanosomiasis, commonly known as sleeping sickness, is one of the world’s most neglected infectious diseases. Spread by tsetse flies, trypanosomes not only cause fatal human infection but also the dreaded Nagana, a veterinary malady with dramatic economic consequences. Trypanosomiasis is an exemplary disease of poverty.African trypanosomes are unicellular, flagellate parasites that thrive in the bloodstream of mammals. Evolution has provided the blood parasite with a unique cell surface coat consisting of a single type of variant surface glycoprotein (VSG). We found that in culture, host-derived antibodies are rapidly removed from the VSG coat. The coordinate action of directional cellular motility and plasma membrane recycling is necessary and sufficient for the clearance of host antibodies.The goal of the proposed project is to explore antibody clearance as virulence factor in the course of natural trypanosome infections and to exploit the knowledge gained for novel therapeutic approaches. We have devised a work plan that requires close collaboration between African and German partners. The experimental approach takes advantage of the distinct expertise and resources available in Nairobi and Darmstadt. Advanced molecular cell biology and infection genetics are combined with live animal experiments, epidemiology and bioinformatics. Obviously, the design of our project entails unique challenges and benefits for the young scientist involved.