Malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro

Arambage, Shashini C; Grant, Karen M.; Pardo, Ian; Ranford-Cartwright, Lisa; Hurd, Hilary

doi:10.1186/1756-3305-2-32

Cited by 43 publications

(53 citation statements)

References 51 publications

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“…A variety of parasitic protozoans such as Trypanosoma, Leishmania, Plasmodium, Toxoplasma, Trichomonas, Blastocystis, Entomoeba and Giardia were reported to be associated with apoptosis (Jiménez-Ruiz et al, 2010;Lüder et al, 2010). Similarly, some ookinetes of Plasmodium also die by a mechanism resembling apoptosis (Arambage et al, 2009). As previously reported, only 50% (or fewer) of A. taiwanensis trophozoites can successfully migrate (Chen, 1999); others usually end up dead, likely through apoptosis according to the present observations of different markers.…”

Section: Discussionsupporting

confidence: 57%

Apoptosis ofAscogregarina taiwanensis(Apicomplexa: Lecudinidae) which failed to migrate within its natural host

Chen

Huang

Fan-Chiang

et al. 2012

Journal of Experimental Biology

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SUMMARYSexual reproduction of Ascogregarina taiwanensis (Apicomplexa: Lecudinidae), a parasite specific to the mosquito Aedes albopictus, in Malpighian tubules is initiated by the entry of the trophotozoites developed in the midgut shortly after pupation (usually <5h). However, only a low proportion of trophozoites are able to migrate; others end up dying. In this study, we demonstrated that those trophozoites that failed to migrate eventually died of apoptosis. Morphological changes such as shrinkage, chromatin aggregations and formation of blunt ridges on the surface were seen in moribund trophozoites. In addition, DNA fragmentation of trophozoites isolated from the midgut of pupae was demonstrated by the presence of DNA ladders, Annexin V staining and TUNEL assays. Detection of caspase-like activity suggests that apoptosis of those trophozoites may have occurred through a mechanism of an intrinsic or mitochondrial-mediated pathway. Although apoptosis has been observed in various protozoan species, it is not clear how apoptosis in single-celled organisms might result from evolution by natural selection. However, we speculate that apoptosis may regulate the parasite load of A. taiwanensis within its natural mosquito host, leading to an optimized state of the survival rate for both parasite and host.Supplementary material available online at

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Section: Discussionsupporting

confidence: 57%

Apoptosis ofAscogregarina taiwanensis(Apicomplexa: Lecudinidae) which failed to migrate within its natural host

Chen

Huang

Fan-Chiang

et al. 2012

Journal of Experimental Biology

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“…This is regarded as a reliable fluorescent probe for use with intact cells [28] and has been used with appropriate controls in previous studies as a marker of apoptosis [7]. Samples were mounted with Vectashield containing DAPI prior to examination.…”

Section: Methodsmentioning

confidence: 99%

Variation in apoptosis mechanisms employed by malaria parasites: the roles of inducers, dose dependence and parasite stages

Matthews

Ali

Carter

et al. 2012

Malar J

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BackgroundPlasmodium berghei ookinetes exhibit an apoptotic phenotype when developing within the mosquito midgut lumen or when cultured in vitro. Markers of apoptosis increase when they are exposed to nitric oxide or reactive oxygen species but high concentrations of hydrogen peroxide cause death without observable signs of apoptosis. Chloroquine and other drugs have been used to induce apoptosis in erythrocytic stages of Plasmodium falciparum and to formulate a putative pathway involving cysteine protease activation and mitochondrial membrane permeabilization; initiated, at least in the case of chloroquine, after its accumulation in the digestive vacuole causes leakage of the vacuole contents. The lack of a digestive vacuole in ookinetes prompted the investigation of the effect of chloroquine and staurosporine on this stage of the life cycle. Finally, the suggestion that apoptosis may have evolved as a strategy employed by ookinetes to increase the fitness of surviving parasites was explored by determining whether increasing the ecological triggers parasite density and nutrient depletion induced apoptosis.MethodsOokinetes were grown in culture then either exposed to hydrogen peroxide, chloroquine or staurosporine, or incubated at different densities and in different media. The proportion of ookinetes displaying positive markers for apoptosis in treated samples was compared with controls and results were analyzed using analysis of variance followed by a Turkey’s test, or a Kruskal-Wallis test as appropriate.ResultsHydrogen peroxide below 50 μM triggered apoptosis but cell membranes were rapidly compromised by higher concentrations, and the mode of death could not be defined. Both chloroquine and staurosporine cause a significant increase in ookinetes with condensed chromatin, caspase-like activity and, in the case of chloroquine, phosphatidylserine translocation and DNA fragmentation (not investigated for staurosporine). However, mitochondrial membrane potential remained intact. No relationship between ookinete density and apoptosis was detected but nutrient depletion significantly increased the proportion of ookinetes with chromatin condensation in four hours.ConclusionsIt is proposed that both a mitochondrial and an amitochondrial apoptotic pathway may be involved, dependent upon the trigger that induces apoptosis, and that pathways may differ between erythrocytic stages and ookinetes, or between rodent and human malaria parasites.

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“…In addition to the putative part played by apoptosis in sex determination of gametocytes, apoptosis is reported to occur during development of oocytes from ookinetes in the mosquito midgut [46] [47]. However, it is interesting to note that this form of apoptosis promotes rather than restricts parasite propagation.…”

Section: Apoptosis Of Malaria Sexual Stagesmentioning

confidence: 97%

Bridging the Knowledge Gap in Transmission-Blocking Immunity to Malaria: Deciphering Molecular Mechanisms in Mosquitoes

Satapathy¹,

Taylor‐Robinson²

2016

AID

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The worldwide decline over the last decade in the number of clinical cases of malaria does not mean an end to the universal problem of malaria pathogenesis in those afflicted by infection. Resistance to drugs, higher risk of disease relapse and failure to maintain effective memory of the pathogen in the absence of persistent exposure result in the repeated failure of anti-malarial treatments. The artificial blocking of transmission of the Plasmodium parasite between hosts from human to Anopheles mosquito, and vice versa, is crucial to restricting the spread of disease. However, a limited knowledge of the molecular mechanisms in operation for transmission of malaria has impeded progress towards a transmission-blocking vaccine. This review highlights the role of anti-malarial immune responses to antigen-specific targets for designing effective vaccines against the sexual stages of Plasmodium that occur within the invertebrate vector. In particular, artificial induction of gametocyte and ookinete apoptosis as a novel means to prevent gamete fertilization and oocyte development, respectively, is highlighted. This and other recent insights into our understanding of the molecular regulation of transmission-blocking immunity are discussed and future prospects considered.

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Malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro

Cited by 43 publications

References 51 publications

Apoptosis ofAscogregarina taiwanensis(Apicomplexa: Lecudinidae) which failed to migrate within its natural host

Apoptosis ofAscogregarina taiwanensis(Apicomplexa: Lecudinidae) which failed to migrate within its natural host

Variation in apoptosis mechanisms employed by malaria parasites: the roles of inducers, dose dependence and parasite stages

Bridging the Knowledge Gap in Transmission-Blocking Immunity to Malaria: Deciphering Molecular Mechanisms in Mosquitoes

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