Environmental Constraints Guide Migration of Malaria Parasites during Transmission

Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. In order to systematically examine how sporozoite migration depends on the structure of the environment, we studied it in micro-fabricated obstacle arrays. The trajectories observed in vivo and in vitro closely resemble each other suggesting that structural constraints can be sufficient to guide Plasmodium sporozoites in complex environments. Sporozoite speed in different environments is optimized for migration and correlates with persistence length and dispersal. However, this correlation breaks down in mutant sporozoites that show adhesion impairment due to the lack of TRAP-like protein (TLP) on their surfaces. This may explain their delay in infecting the host. The flexibility of sporozoite adaption to different environments and a favorable speed for optimal dispersal ensures efficient host switching during malaria transmission.在复杂环境中，迁移细胞主要通过趋化作用或周围组织提供的结构线索获得引导。在疟疾传播过程中，皮肤内的寄生虫运动能力对于疟原虫（Plasmodium）子孢子（sporozoite）抵达血液循环系统至关重要。本研究发现，子孢子的迁移行为会因疟原虫在蚊虫叮咬的任意部位所遭遇的不同皮肤环境而存在差异。为系统性探究子孢子迁移如何依赖于环境结构，我们在微加工障碍阵列中对其展开了研究。体内（in vivo）与体外（in vitro）观测到的运动轨迹高度相似，这表明结构约束足以在复杂环境中引导疟原虫子孢子的迁移。不同环境中的子孢子运动速度均适配迁移需求，且与运动持续长度及扩散能力存在相关性。然而，因表面缺乏类TRAP蛋白（TRAP-like protein, TLP）而出现黏附功能受损的突变型子孢子，其运动速度与上述指标的相关性不复存在。这或可解释此类突变型子孢子感染宿主时出现的延迟现象。子孢子对不同环境的适应灵活性，以及适配最优扩散的运动速度，共同保障了疟疾传播过程中高效的宿主转换。