The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites.
The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites.
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DOI：
10.1038/ncomms11659
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发表时间：
2016-05-26
影响因子：
16.6
通讯作者：
Spielmann T
中科院分区：
文献类型：
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作者：
De Niz M;Ullrich AK;Heiber A;Blancke Soares A;Pick C;Lyck R;Keller D;Kaiser G;Prado M;Flemming S;Del Portillo H;Janse CJ;Heussler V;Spielmann T
被人类疟疾寄生虫恶性疟原虫感染的红细胞在器官（如大脑）中的隔离被认为是致病性的重要因素。在使用啮齿类寄生虫伯氏疟原虫的疟疾小鼠模型中也观察到了类似的现象，但目前尚不清楚已知参与这一过程的恶性疟原虫蛋白质是否在啮齿类寄生虫中保守。在这里，我们确定了恶性疟原虫的两个关键因子SBP1和MAHRP1的伯氏疟原虫直系同源物。感染缺乏SBP1或MAHRP1a的伯氏疟原虫的红细胞不能结合内皮受体CD36，并在小鼠中显示出降低的隔离和毒力。突变的伯氏疟原虫寄生虫与相应的恶性疟原虫SBP 1和MAHRP 1直系同源物的互补恢复了隔离和毒力。这些发现揭示了不同疟原虫隔离机制的进化保守性，并支持伯氏疟原虫啮齿动物模型是研究疟疾毒力的适当工具的观点。 人疟原虫的蛋白质SBP 1和MAHRP 1是隔离主要器官中受感染的红细胞所必需的。在这里，De Niz等人鉴定了啮齿类寄生虫伯氏疟原虫中的同源蛋白质，表明它们起着类似的作用，并支持疟疾小鼠模型的有用性。
Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence. Proteins SBP1 and MAHRP1 of the human malaria parasite are required for sequestration of infected red blood cells in major organs. Here, De Niz et al. identify homologous proteins in the rodent parasite Plasmodium berghei, showing that they play similar roles and supporting the usefulness of malaria mouse models.