Pro- and anti-apoptotic activities of protozoan parasites.
ABSTRACT During infection, programmed cell death, i.e. apoptosis, is an important effector mechanism of innate and adaptive host responses to parasites. In addition, it fulfils essential functions in regulating host immunity and tissue homeostasis. Not surprisingly, however, adaptation of parasitic protozoa to their hosts also involves modulation or even exploitation of cell death in order to facilitate parasite survival in a hostile environment. During recent years, considerable progress has been made in our understanding of apoptosis during parasitic infections and there is now convincing evidence that apoptosis and its modulation by protozoan parasites has a major impact on the parasite-host interaction and on the pathogenesis of disease. This review updates our current knowledge on the diverse functions apoptosis may fulfil during infections with diverse protozoan parasites including apicomplexans, kinetoplastids and amoebae. Furthermore, we also summarize common mechanistic themes of the pro- and anti-apoptotic activities of protozoan parasites. The diverse and complex effects which parasitic protozoa exert on apoptotic cell death within the host highlight fascinating interactions of parasites and their hosts. Importantly, they also stress the importance of further investigations before the modulation of host cell apoptosis can be exploited to combat parasitic infections.
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ABSTRACT: Programmed cell death leading to apoptosis is essential for normal development and homeostasis in plants and throughout the animal kingdom. Although there are differences in apoptotic mechanisms between lower animals and vertebrates, crucial biochemical components of the programmed cell death pathways remained remarkably conserved throughout evolution. Despite decades of studies on the neurobiology and development of mollusks, comparatively little is known about the mechanisms of apoptosis in this phylum. In this review, an attempt is made to summarize data obtained on mollusks so far, and to discuss the molecular mechanisms, the functional and ecological significance of apoptosis and the advantages of snail preparations as tools for programmed cell death research. A definitive comparison of the data obtained on mollusks with those obtained on the more widely studied vertebrates, will contribute to the better understanding of the apoptotic process in general and of its evolutionary development.Apoptosis 03/2010; 15(3):313-21. · 4.07 Impact Factor
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ABSTRACT: In the present study we addressed the question whether Toxoplasma gondii could promote apoptosis in T lymphocytes in the acute stage of infection. Using in vivo activated T cells and then culturing them for a short time, we observed activation-induced cell death in T. gondii infected mice. A higher level of activation-induced cell death (AICD) was seen in susceptible C57BL/6 mice than in resistant CBA/J mice following infection with the same P strain of parasite. Apoptosis in T cells of susceptible mice was associated with altered induction of Bcl-2/Bax, loss of Mitochondrial Transmembrane Potential. Both CD4+ and CD8+ T cells were found to be susceptible to apoptosis; CD4+ T cells were sensitive to Fas-mediated death whereas CD8+ T cells were insensitive to this signal. Caspase inhibitors had less effect on DNA fragmentation in CD4+ compared to CD8+ T cells. Exposure of CD4+ T cells to anti-IFNgamma mAb resulted in an increase in the number of T cells that were positive for anti-apoptotic molecule Bcl-2 and DiOC6, a cationic dye that accumulates in intact mitochondria. These changes were less noticeable in CD8+ T cells following treatment with anti-IFNgamma mAb. These findings provide further insight into the mechanisms of T cell apoptosis in T. gondii infection.Microbial Pathogenesis 09/2009; 47(5):281-8. · 1.97 Impact Factor
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ABSTRACT: Macrophages (Mφ) and dendritic cells are the major target cell populations of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. Leishmania promastigotes have been shown to protect Mφ, neutrophils, and dendritic cells from both natural and induced apoptosis. Nevertheless, the effect of the infection with Leishmania amastigotes in the apoptosis of these cell populations has not been established, which results are very important since amastigotes persist in cells for many days and are responsible for sustaining infection in the host. As shown in this study, apoptosis of monocyte-derived dendritic cells (moDC) induced by treatment with camptothecin was downregulated by infection with L. mexicana amastigotes from 42.48 to 36.92 % as detected by Annexin-V binding to phosphatidylserine. Also, the infection of moDC with L. mexicana amastigotes diminished the fragmentation of DNA as detected by terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling assay, and changes in cell morphology were analyzed by electron microscopy. The observed antiapoptotic effect was found to be associated with an 80 % reduction in the presence of active caspase-3 in infected moDC. The capacity of L. mexicana amastigotes to delay apoptosis induction in the infected moDC may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.Parasitology Research 02/2013; · 2.85 Impact Factor