Plasmodium falciparum exhibits markers of regulated cell death at high population density in vitro
Plasmodium falciparum exhibits markers of regulated cell death at high population density in vitro
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DOI：
10.1016/j.parint.2016.07.007
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发表时间：
2016-12-01
影响因子：
1.9
通讯作者：
Coetzer, Theresa Louise
中科院分区：
文献类型：
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作者：
Engelbrecht, Dewaldt;Coetzer, Theresa Louise
原生动物寄生虫恶性疟原虫的无性红细胞周期是疟疾发病的原因，并导致绝大多数疟疾死亡。在这48小时周期内迅速增加的寄生虫血症威胁到人类宿主的生存，并在将缓慢成熟的性阶段传播给蚊子宿主之前威胁到寄生虫。寄生虫可以利用调节性细胞死亡（RCD）来控制宿主的感染负担，从而帮助其自身的生存和传播。恶性疟原虫中RCD的发生仍然是一个有争议的话题。我们提供了强有力的证据，在恶性疟原虫的寄生虫密度高的条件下，发生的RCD的寄生虫病样表型。将恶性疟原虫保持在体外，并通过允许其生长至不受限制的寄生虫血症峰值来进行应激。细胞死亡标志物，包括形态学变化、DNA片段化、线粒体极化和磷脂酰丝氨酸外化，用于在寄生虫血症高峰时和24小时后检测寄生虫死亡。在寄生虫血症高峰期，观察到线粒体去极化，以及在寄生虫和相邻的未感染的红细胞中的磷脂酰丝氨酸外化。DNA片段化与寄生虫血症的下降相吻合。在寄生虫高峰期，在成熟的寄生虫中观察到较少的裂殖子。在两个红细胞内周期内观察到生长恢复至近峰值寄生虫血症。细胞死亡的生化标志物的组合和时间顺序表明发生了类骨化症表型。恶性疟原虫中RCD途径的鉴定可能提供新的药物靶点，特别是如果该途径与宿主机制不同的话。(C)2016爱思唯尔爱尔兰有限公司版权所有。
The asexual erythrocytic cycle of the protozoan parasite Plasmodium falciparum is responsible for the pathogenesis of malaria and causes the overwhelming majority of malaria deaths. Rapidly increasing parasitaemia during this 48 hour cycle threatens the survival of the human host and the parasite prior to transmission of the slow-maturing sexual stages to the mosquito host. The parasite may utilise regulated cell death (RCD) to control the burden of infection on the host and thus aid its own survival and transmission. The occurrence of RCD in P. falciparum remains a controversial topic. We provide strong evidence for the occurrence of an apoptosis-like phenotype of RCD in P. falciparum under conditions of high parasite density. P. falciparum was maintained in vitro and stressed by allowing growth to an unrestricted peak parasitaemia. Cell death markers, including morphological changes, DNA fragmentation, mitochondria] polarisation and phosphatidylserine externalisation were used to characterise parasite death at the time of peak parasitaemia and 24 h later. At peak parasitaemia, mitochondrial depolarisation was observed, together with phosphatidylserine externalisation in both parasitised- and neighbouring non-infected erythrocytes. DNA fragmentation coincided with a decline in parasitaemia. Fewer merozoites were observed in mature schizonts at peak parasitaemia. Growth recovery to near-peak parasitaemia was noted within two intraerythrocytic cycles. The combination and chronological order of the biochemical markers of cell death suggest the occurrence of an apoptosis-like phenotype. The identification of a RCD pathway in P. falciparum may provide novel drug targets, particularly if the pathway differs from the host machinery. (C) 2016 Elsevier Ireland Ltd. All rights reserved.