Plasmodium falciparum exhibits markers of regulated cell death at high population density in vitro

被引:18
作者
Engelbrecht, Dewaldt [1 ]
Coetzer, Theresa Louise [1 ,2 ]
机构
[1] Univ Witwatersrand, Fac Hlth Sci, Sch Pathol, Wits Res Inst Malaria,Dept Mol Med & Haematol, Johannesburg, South Africa
[2] Natl Hlth Lab Serv, Johannesburg, South Africa
基金
新加坡国家研究基金会;
关键词
Regulated cell death; Plasmodium falciparum; High parasitaemia; DNA fragmentation; Mitochondrial depolarisation; Phosphatidylserine externalisation; ASEXUAL BLOOD STAGES; MALARIA PARASITE; FEBRILE TEMPERATURE; PROTOZOAN PARASITES; INDUCED APOPTOSIS; CAUTIONARY NOTE; TUNEL ASSAY; MEMBRANE; PHOSPHATIDYLSERINE; NECROSIS;
D O I
10.1016/j.parint.2016.07.007
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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.
引用
收藏
页码:715 / 727
页数:13
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