Time-lapse imaging of red blood cell invasion by the rodent malaria parasite Plasmodium yoelii.

Time-lapse imaging of red blood cell invasion by the rodent malaria parasite Plasmodium yoelii.
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DOI:
10.1371/journal.pone.0050780
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kaneko O
Kaneko O
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yahata K;Treeck M;Culleton R;Gilberger TW;Kaneko O

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为了在哺乳动物宿主中繁殖,疟原虫必须侵入红细胞(RBC)。这一过程为用药物或疫苗靶向寄生虫提供了机会。然而,大多数与RBC侵袭相关的研究都分析了寄生虫蛋白与宿主细胞在静态条件下的分子相互作用,这些相互作用的动力学在很大程度上仍未研究。红细胞侵入的延时成像是研究细胞侵入的有力技术,并已报道用于诺氏疟原虫和恶性疟原虫。然而,遗传基因座的实验性修饰对于这些物种来说是费力且耗时的。我们已经建立了一个系统的时间推移成像的啮齿动物疟原虫约氏疟原虫,其中修改的遗传位点更快,更简单。我们比较了约氏疟原虫和恶性疟原虫侵入红细胞的动力学,发现侵入过程中的总体动力学相似,但有一些例外。这些差异中最显著的是,在从RBC排出后,约氏疟原虫裂殖子的形状逐渐从扁平细长的椭圆形变为球形体,该过程需要约60秒。在此期间,裂殖子能够附着在RBC膜上并使其变形,但不能重新定向和侵入。我们推测约氏疟原虫裂殖子的这种形态学变化可能与其分泌或激活入侵相关蛋白有关。因此,约氏疟原虫裂殖子似乎是一个很好的模型,以分析红细胞入侵的分子动力学,特别是在形态过渡阶段,这可以作为一个扩展的窗口,不能观察到恶性疟原虫。
In order to propagate within the mammalian host, malaria parasites must invade red blood cells (RBCs). This process offers a window of opportunity in which to target the parasite with drugs or vaccines. However, most of the studies relating to RBC invasion have analyzed the molecular interactions of parasite proteins with host cells under static conditions, and the dynamics of these interactions remain largely unstudied. Time-lapse imaging of RBC invasion is a powerful technique to investigate cell invasion and has been reported for Plasmodium knowlesi and Plasmodium falciparum. However, experimental modification of genetic loci is laborious and time consuming for these species. We have established a system of time-lapse imaging for the rodent malaria parasite Plasmodium yoelii, for which modification of genetic loci is quicker and simpler. We compared the kinetics of RBC invasion by P. yoelii with that of P. falciparum and found that the overall kinetics during invasion were similar, with some exceptions. The most striking of these differences is that, following egress from the RBC, the shape of P. yoelii merozoites gradually changes from flat elongated ovals to spherical bodies, a process taking about 60 sec. During this period merozoites were able to attach to and deform the RBC membrane, but were not able to reorient and invade. We propose that this morphological change of P. yoelii merozoites may be related to the secretion or activation of invasion-related proteins. Thus the P. yoelii merozoite appears to be an excellent model to analyze the molecular dynamics of RBC invasion, particularly during the morphological transition phase, which could serve as an expanded window that cannot be observed in P. falciparum.
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