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High speed, three-dimensional imaging reveals chemotactic behavior specific to human-infective Leishmania parasites
bioRxiv - Biophysics Pub Date : 2020-07-31 , DOI: 10.1101/2020.07.30.220541
Rachel C Findlay , Mohamed Osman , Kirstin Spence , Paul M. Kaye , Pegine B. Walrad , Laurence G. Wilson

Cellular motility is an ancient eukaryotic trait, ubiquitous across phyla with roles in predator avoidance, resource access and competition. Flagellar-dependent motility is seen in a variety of parasitic protozoans and morphological changes in flagellar structure and function have been qualitatively described during differentiation. However, whether the dynamics of flagellar motion vary across lifecycle stages and whether such changes serve to facilitate human infection is not known. Here we used holographic video microscopy to study the pattern of motility in insect midgut forms of Leishmania (procyclic promastigotes; PCF) and differentiated human infective metacyclic promastigotes (META). We discovered that PCF swim in a slow, corkscrew motion around a gently curving axis while META display run and tumble behaviour in the absence of stimulus, reminiscent of bacterial behaviour. In addition, we demonstrate that META specifically respond to a macrophage-derived stimulus, modifying swimming direction and speed to target host immune cells. Thus, the motility strategy employed by Leishmania appears as a random search that is replaced with a ballistic swimming motion in the presence of an immunological stimulus. These findings shed unique insights into how flagellar motion adapts to the particular needs of the parasite at different times in its lifecycle and define a new pre-adaptation for infection of the human host.

中文翻译:

高速三维成像显示特定于人类感染利什曼原虫的趋化行为

细胞运动性是一种古老的真核生物特征,在整个门上无处不在,在避免捕食,资源获取和竞争中发挥作用。鞭毛依赖的运动性在各种寄生原生动物中可见,并且在分化过程中定性地描述了鞭毛结构和功能的形态变化。然而,鞭毛运动的动力学在生命周期的各个阶段是否有所不同,以及这种变化是否有助于人类感染尚不清楚。在这里,我们使用全息视频显微镜研究了利什曼原虫昆虫中肠形式的运动模式(前环前鞭毛体; PCF)和分化的人类感染性元环前鞭毛体(META)。我们发现PCF在缓慢弯曲的轴上以缓慢的开瓶器运动游泳,而META在没有刺激的情况下显示运行和翻滚行为,让人联想到细菌的行为。另外,我们证明了META对巨噬细胞衍生的刺激有特异性反应,改变游泳方向和速度以靶向宿主免疫细胞。因此,利什曼原虫采用的运动策略出现为随机搜索,在有免疫刺激的情况下被弹道游泳运动所取代。这些发现为鞭毛运动如何在其生命周期的不同时间适应寄生虫的特殊需求提供了独特的见解,并为人类宿主的感染定义了新的预适应。
更新日期:2020-08-01
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