Sunlight inhibits growth and induces markers of programmed cell death in Plasmodium falciparum in vitro

Dewaldt Engelbrecht,Thérèsa Louise Coetzer

doi:10.1186/s12936-015-0867-0

Dewaldt Engelbrecht, Thérèsa Louise Coetzer

Open Access

https://doi.org/10.1186/s12936-015-0867-0

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Abstract

BackgroundPlasmodium falciparum is responsible for the majority of global malaria deaths. During the pathogenic blood stages of infection, a rapid increase in parasitaemia threatens the survival of the host before transmission of slow-maturing sexual parasites to the mosquito vector to continue the life cycle. Programmed cell death (PCD) may provide the parasite with the means to control its burden on the host and thereby ensure its own survival. Various environmental stress factors encountered during malaria may induce PCD in P. falciparum. This study is the first to characterize parasite cell death in response to natural sunlight.MethodsThe 3D7 strain of P. falciparum was cultured in vitro in donor erythrocytes. Synchronized and mixed-stage parasitized cultures were exposed to sunlight for 1 h and compared to cultures maintained in the dark, 24 h later. Mixed-stage parasites were also subjected to a second one-hour exposure at 24 h and assessed at 48 h. Parasitaemia was measured daily by flow cytometry. Biochemical markers of cell death were assessed, including DNA fragmentation, mitochondrial membrane polarization and phosphatidylserine externalization.ResultsSunlight inhibited P. falciparum growth in vitro. Late-stage parasites were more severely affected than early stages. However, some late-stage parasites survived exposure to sunlight to form new rings 24 h later, as would be expected during PCD whereby only a portion of the population dies. DNA fragmentation was observed at 24 and 48 h and preceded mitochondrial hyperpolarization in mixed-stage parasites at 48 h. Mitochondrial hyperpolarization likely resulted from increased oxidative stress. Although data suggested increased phosphatidylserine externalization in mixed-stage parasites, results were not statistically significant.ConclusionThe combination of biochemical markers and the survival of some parasites, despite exposure to a lethal stimulus, support the occurrence of PCD in P. falciparum.

Highlights

Plasmodium falciparum is responsible for the majority of global malaria deaths
Sunlight inhibited Plasmodium falciparum growth in vitro Mixed and synchronized parasite cultures were exposed to one hour of sunlight and assessed for growth 24 h later
Twenty-four hours after a single exposure, ring stage parasites in both mixed stage (Fig. 1aii, bii) and synchronized (Fig. 2aii, bii) parasites progressed to trophozoite stages (Figs. 1aiv, biv, 2aiv, biv, respectively) similar to control cultures maintained in the dark (Figs. 1aiii, biii, 2aiii, biii, respectively)

Summary

Introduction

Plasmodium falciparum is responsible for the majority of global malaria deaths. During the pathogenic blood stages of infection, a rapid increase in parasitaemia threatens the survival of the host before transmission of slow-maturing sexual parasites to the mosquito vector to continue the life cycle. PCD may be induced by a number of environmental stress factors encountered by the parasite during malaria illness, including high parasite population density [9] and febrile episodes [10,11,12]. The considerable cardiac output delivered to cutaneous circulation [13] means that at any one time a significant number of intra-erythrocytic parasites are located in the superficial blood vessels, and are exposed to penetrating solar radiation. This proportion may further increase as a result of vasodilation during fever paroxysms [14]

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