Early gametocytes of the malaria parasite Plasmodium falciparum specifically remodel the adhesive properties of infected erythrocyte surface
Early gametocytes of the malaria parasite Plasmodium falciparum specifically remodel the adhesive properties of infected erythrocyte surface
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DOI：
10.1111/cmi.12062
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Alano, Pietro
中科院分区：
文献类型：
--
作者：
Tiburcio, Marta;Silvestrini, Francesco;Alano, Pietro
在恶性疟原虫感染的寄生虫传播阶段，配子体在10天内成熟，被隔离在内脏器官中。最近的研究表明，在配子体成熟过程中，细胞的机械特性而不是粘附相互作用在隔离中起作用。相反，它仍然不清楚隔离是如何建立的，以及在配子体发生开始时，与无性滋养体形态相似的最早的性阶段是如何改变受感染的红细胞及其细胞粘附特性的。本研究利用纯化的恶性疟原虫早期配子体对疟原虫在红细胞表面诱导的修饰进行超微结构和生化分析，并测量其对人内皮细胞粘附的功能影响。这项工作揭示了I期配子体能够像无性寄生虫一样使被感染的红细胞变形，但不会用粘性旋钮结构和相关蛋白修饰其表面。这些寄生虫暴露在红细胞表面的恶性疟原虫红细胞膜蛋白1 （PfEMP1）粘附素水平降低，并且var基因家族（编码5060个PfEMP1变异）的表达在从无性发育到配子细胞发生的转变中显著下调。细胞粘附实验表明，这种基因表达变化和宿主细胞表面修饰在功能上导致I期配子体无法结合宿主配体，而宿主配体是无性寄生体结合内皮细胞所使用的。总之，这些结果确定了宿主细胞重塑的分子和细胞机制以及粘附特性的特定差异，从而导致宿主寄生虫在建立I期配子体和无性滋养体的隔离方面具有明显不同的相互作用。
In Plasmodium falciparum infections the parasite transmission stages, the gametocytes, mature in 10 days sequestered in internal organs. Recent studies suggest that cell mechanical properties rather than adhesive interactions play a role in sequestration during gametocyte maturation. It remains instead obscure how sequestration is established, and how the earliest sexual stages, morphologically similar to asexual trophozoites, modify the infected erythrocytes and their cytoadhesive properties at the onset of gametocytogenesis. Here, purified P.falciparum early gametocytes were used to ultrastructurally and biochemically analyse parasite-induced modifications on the red blood cell surface and to measure their functional consequences on adhesion to human endothelial cells. This work revealed that stage I gametocytes are able to deform the infected erythrocytes like asexual parasites, but do not modify its surface with adhesive knob' structures and associated proteins. Reduced levels of the P.falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins are exposed on the red blood cell surface bythese parasites, and the expression of the var gene family, which encodes 5060 variants of PfEMP1, is dramatically downregulated in the transition from asexual development to gametocytogenesis. Cytoadhesion assays show that such gene expression changes and host cell surface modifications functionally result in the inability of stage I gametocytes to bind the host ligands used by the asexual parasite to bind endothelial cells. In conclusion, these results identify specific differences in molecular and cellular mechanisms of host cell remodelling and in adhesive properties, leading to clearly distinct host parasite interplays in the establishment of sequestration of stage I gametocytes and of asexual trophozoites.