%0 Journal Article
%T On Programmed Cell Death in Plasmodium falciparum: Status Quo
%A Dewaldt Engelbrecht
%A Pierre Marcel Durand
%A Th¨¦r¨¨sa Louise Coetzer
%J Journal of Tropical Medicine
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/646534
%X Conflicting arguments and results exist regarding the occurrence and phenotype of programmed cell death (PCD) in the malaria parasite Plasmodium falciparum. Inconsistencies relate mainly to the number and type of PCD markers assessed and the different methodologies used in the studies. In this paper, we provide a comprehensive overview of the current state of knowledge and empirical evidence for PCD in the intraerythrocytic stages of P. falciparum. We consider possible reasons for discrepancies in the data and offer suggestions towards more standardised investigation methods in this field. Furthermore, we present genomic evidence for PCD machinery in P. falciparum. We discuss the potential adaptive or nonadaptive role of PCD in the parasite life cycle and its possible exploitation in the development of novel drug targets. Lastly, we pose pertinent unanswered questions concerning the PCD phenomenon in P. falciparum to provide future direction. 1. Introduction Programmed cell death (PCD) forms an integral physiological part of multicellular organisms, where it plays an essential role in normal development and maintenance of integrity and homeostasis. In addition, it forms part of the defense response to combat infectious pathogens as well as being involved in the pathogenesis of certain human diseases (reviewed in [1¨C3]). This self-sacrificial cell-death phenomenon has also been demonstrated in unicellular organisms, including parasitic protozoa (reviewed in [4, 5]). Apart from the ability to orchestrate their own death, parasites can facilitate their development and survival by inducing PCD in host cells (reviewed in [6]). These host-pathogen interactions are complex, and the role of PCD in balancing pathogenic and survival mechanisms remains poorly understood. The definitions of PCD and its various phenotypes are considered in Table 2 of Appendix A. Observations of PCD have their foundations in the middle-late nineteenth century as an awareness of physiological cell death [7, 8] although the term was first coined in 1964 by Lockshin and Williams [9]. Apoptosis, now recognised as a prominent phenotype of PCD, was described in 1972 by Kerr and coworkers [10]. More than 20 years later, apoptosis was demonstrated in a unicellular trypanosome [11], and in 1997, it was described in two species of malaria parasites, Plasmodium falciparum [12] and P. yoelii [13]. Different phenotypes of PCD have been shown in evolutionary diverse unicellular eukaryote lineages [14, 15] as well as in prokaryotes [16]. However, a growing body of conflicting evidence regarding PCD
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