The malaria parasite Plasmodium falciparum in red blood cells selectively takes up serum proteins that affect host pathogenicity
The malaria parasite Plasmodium falciparum in red blood cells selectively takes up serum proteins that affect host pathogenicity
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DOI：
10.1186/s12936-020-03229-1
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发表时间：
2020-04-15
期刊：
影响因子：
3
通讯作者：
Horii, Toshihiro
中科院分区：
文献类型：
--
作者：
Tougan, Takahiro;Edula, Jyotheeswara R.;Horii, Toshihiro
疟疾寄生虫恶性疟原虫是一种在红细胞中发育的原生动物，需要多种宿主因子。为了在红细胞中发育，不仅需要从红细胞胞浆中获取营养，还需要从细胞外环境中获取营养。虽然恶性疟原虫对宿主营养物质的利用已被广泛分析，但只有少数研究报道了其对宿主血清蛋白的利用。因此，本研究的目的是全面鉴定恶性疟原虫所吸收的宿主血清蛋白，并阐明其在发病机制中的作用。方法用人血清体外培养恶性疟原虫。采用霰弹枪液相色谱-质谱法/质谱法和western blotting综合测定寄生虫对血清蛋白的摄取。测定血清钙离子浓度，测定寄生虫裂解液凝血活性。结果在足够的Ca2+水平下，维生素k依赖性蛋白S、凝血酶原和玻璃体粘连蛋白3种蛋白被选择性内化。这些蛋白质的摄取在DNA复制之前就开始了，并且在滋养体和分裂体阶段增加，与肌动蛋白丝的组装/拆卸无关。凝血试验显示，凝血酶原被激活，从而诱导血液凝固。结论在足够Ca2+水平的培养条件下，寄生虫对血清蛋白的吸收。这种摄取现象与它们的致病性有关。
Background The malaria parasite Plasmodium falciparum is a protozoan that develops in red blood cells (RBCs) and requires various host factors. For its development in RBCs, nutrients not only from the RBC cytosol but also from the extracellular milieu must be acquired. Although the utilization of host nutrients by P. falciparum has been extensively analysed, only a few studies have reported its utilization of host serum proteins. Hence, the aim of the current study was to comprehensively identify host serum proteins taken up by P. falciparum parasites and to elucidate their role in pathogenesis. Methods Plasmodium falciparum was cultured with human serum in vitro. Uptake of serum proteins by parasites was comprehensively determined via shotgun liquid chromatography-mass spectrometry/mass spectrometry and western blotting. The calcium ion concentration in serum was also evaluated, and coagulation activity of the parasite lysate was assessed. Results Three proteins, vitamin K-dependent protein S, prothrombin, and vitronectin, were selectively internalized under sufficient Ca2+ levels in the culture medium. The uptake of these proteins was initiated before DNA replication, and increased during the trophozoite and schizont stages, irrespective of the assembly/disassembly of actin filaments. Coagulation assay revealed that prothrombin was activated and thereby induced blood coagulation. Conclusions Serum proteins were taken up by parasites under culture conditions with sufficient Ca2+ levels. This uptake phenomenon was associated with their pathogenicity.