Antibody clearance and trans-sialylation as virulence factors in African trypanosomiasis

锥虫是撒哈拉以南非洲人类福祉的主要威胁。它们由臭名昭著的采采蝇传播，感染范围广泛的动物，包括人和牛。我们已经证明，寄生虫在宿主体内的存活得益于鞭毛的持续运动和快速的内吞作用。这两个过程结合在一起，将宿主抗体从锥虫细胞表面移除。我们已经成功地在单细胞水平上以毫秒级的精度详细描述了锥虫在体外和宿主多样化和拥挤的环境中的游泳模式。我们发现，不同的锥虫物种已经适应了不同的感染环境，如循环或组织空间。他们已经进化出一种特殊的细胞波形，允许完美的作废。锥虫是个例外，因为它的游泳技术很差。这个物种进化出了一种不同的生存策略：它使用红细胞附着和反式唾液酸化来逃避免疫破坏。我们将破译弓形虫与宿主细胞相互作用的分子和生物力学机制。最后，我们将使用冷血宿主尼罗河巨蜥来挑战我们的抗体清除和细胞波形假说。

Trypanosomes are a major threat to human welfare in sub-saharan Africa. Transmitted by the infamous tsetse fly, they infect a broad range of animals, including humans and cattle. We have shown that survival of the parasite in the host is aided by incessant flagellar motility and rapid endocytosis. Both processes combined remove host antibodies from the trypanosome cell surface. We have succeeded in detailing, on the single cell level and with millisecond accuracy, the mode of trypanosome swimming in vitro and in the diverse and crowded environments of the host. We show that different trypanosome species have adapted to distinct infection niches, such as the circulation or tissue spaces. They have evolved a special cellular waveform that allows perfect annidation. Trypanosoma congolense is an exception as it is a bad swimmer. This species has evolved a different survival strategy: it uses erythrocyte attachment and trans-sialylation to escape immune destruction. We will decipher the molecular and biomechanical mechanisms behind T. congolense interaction with host cells. Finally, we will challenge our antibody clearance and cellular waveform hypotheses using a cold-blooded host, the Nile monitor lizard.