Imaging Host Cell-Leishmania Interaction Dynamics Implicates Parasite Motility, Lysosome Recruitment, and Host Cell Wounding in the Infection Process
Imaging Host Cell-Leishmania Interaction Dynamics Implicates Parasite Motility, Lysosome Recruitment, and Host Cell Wounding in the Infection Process
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DOI：
10.1016/j.chom.2011.03.011
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发表时间：
2011-04-21
影响因子：
30.3
通讯作者：
Spaeth, Gerald F.
中科院分区：
文献类型：
--
作者：
Forestier, Claire-Lise;Machu, Christophe;Spaeth, Gerald F.
杜氏利什曼原虫引起人类内脏利什曼病。寄生虫感染周期包括在昆虫载体内增殖的细胞外有鞭毛的前鞭毛体和在感染的宿主细胞内繁殖的细胞内不运动的无鞭毛体。使用原代巨噬细胞感染毒性代谢前鞭毛体和高时空分辨率显微镜，我们解剖的早期感染过程的动态。我们发现，能动的前鞭毛体进入巨噬细胞在一个极化的方式通过其鞭毛尖端，并被吞噬到主机溶酶体隔间。持续的细胞内鞭毛活动导致寄生虫鞭毛向宿主细胞外周重新定向，并导致振荡寄生虫运动。后者与局部溶酶体胞吐和宿主细胞质膜损伤有关。这些发现暗示溶酶体募集，随后是溶酶体胞吐，与寄生虫驱动的宿主细胞损伤一致，是利什曼原虫宿主细胞感染中的关键细胞事件。这项工作突出了前鞭毛体的极性和运动在寄生虫进入的作用。
Leishmania donovani causes human visceral leishmaniasis. The parasite infectious cycle comprises extracellular flagellated promastigotes that proliferate inside the insect vector, and intracellular nonmotile amastigotes that multiply within infected host cells. Using primary macrophages infected with virulent metacyclic promastigotes and high spatiotemporal resolution microscopy, we dissect the dynamics of the early infection process. We find that motile promastigotes enter macrophages in a polarized manner through their flagellar tip and are engulfed into host lysosomal compartments. Persistent intracellular flagellar activity leads to reorientation of the parasite flagellum toward the host cell periphery and results in oscillatory parasite movement. The latter is associated with local lysosomal exocytosis and host cell plasma membrane wounding. These findings implicate lysosome recruitment followed by lysosome exocytosis, consistent with parasite-driven host cell injury, as key cellular events in Leishmania host cell infection. This work highlights the role of promastigote polarity and motility during parasite entry.