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: Severity of disease in human African try-panosomiasis may be linked, as in other human protozoan infections, to apoptosis of host inflammatory cells during infection. The present study investigates the involvement of leukocyte apoptosis in Trypanosoma brucei infection of rodents. Twenty-seven Wistar rats were infected with 1 × 10 3 T. brucei and leukocyte apoptosis was evaluated by several methods. Apoptotic cell count was performed in blood, spleen, thymus, lymph node and liver during infections, using Light Microscopy (LM), agarose gel electrophoresis and Transmission Electron Microscopy (TEM). Blood and tissues leukocyte apoptosis in infected animals were confirmed by LM, TEM, and agarose gel electrophoresis, which showed low molecular weight DNA fragments. Infected rats sacrificed after day 8 PI showed sig-nificant increase in apoptotic cells in both blood (p < 0.001) and spleen (p < 0.05). Peak blood leukocyte apoptosis corresponded with peak parasitemia and the lowest total leukocyte count in all infected rats. Our data provide the first documentation of increased levels of blood leukocyte apoptosis during T. brucei infection. Apoptosis of blood cells during trypanosome infection may represent a putative mechanism for the severity of leukopenia and disease. 1 Introduction African Trypanosomiasis is a major zoonotic disease that detrimentally affects both humans and animals. Fifty to sev-enty thousand people are estimated to be afflicted by human African trypanosomiasis (HAT) . The disease in humans is universally fatal without treatment. In some areas, the mortality related to HAT is estimated to be in excess of 1000 cases per year . The morbidity and mortality associated with African trypanosomiasis and the severe productivity losses in livestock have a major economic impact in sub-Saharan Africa including the exclusion of use of land due to Glossina fly habitats.Journal of neuroparasitology 01/2012; 3. DOI:10.4303/jnp/N120101
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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. DOI:10.1016/j.micpath.2009.09.004 · 2.00 Impact Factor
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ABSTRACT: This review is a historical look at work carried out over the past 50 years examining interactions of Toxoplasma with the host cell and attempts to focus on some of the seminal experiments in the field. This early work formed the foundation for more recent studies aimed at identifying the host and parasite factors mediating key Toxoplasma–host cell interactions. We focus especially on those studies that were performed in vitro and provide discussions of the following general areas: (i) establishment of the parasitophorous vacuole, (ii) the requirement of specific host cell molecules for parasite replication, (iii) the scenarios under which the host cell can resist parasite replication and/or persistence, (iv) host species-specific and host strain-specific responses to Toxoplasma infection, and (v) Toxoplasma-induced immune modulation.International journal for parasitology 03/2009; DOI:10.1016/j.ijpara.2009.01.008 · 3.40 Impact Factor