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.

Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked byToxoplasma gondiiPrimarily via Interference with the Mitochondrial Amplification Loop

“…The inhibition of host cell apoptosis is one of the hallmarks of the interaction of intracellular microorganisms with their host cells (3,21,31). The critical importance of apoptosis as antimicrobial effector mechanism makes its parasite-mediated inhibition a promising novel target to combat various infectious diseases that are caused by intracellular pathogens.…”

“…After infection, T. gondii renders host cells resistant to apoptosis induced by various proapoptotic stimuli (3,21,31). This is assumed to be a crucial adaptation of the parasite to its lifestyle that allows sustained intracellular survival and establishing of long-term persistence within its hosts, including up to 30% of humans worldwide.…”

Apoptosis and its functional significance in molluscs

“…Apoptosis plays a key role in defense against protozoan parasites and pathogens and during environmental toxicity caused by different pollutants and toxicants both in vertebrates and invertebrates [8,9]. Recently a comprehensive account was given by Sokolova [10] of the mechanisms and signaling pathway underlying apoptosis in molluscan immune defense.…”

Targeting caspases in intracellular protozoan infections

“…(14)(15)(16)(17)(18)(19) Recent reports show that protozoan parasites target caspases to inhibit apoptosis induced through either extrinsic or intrinsic pathways. Whereas virus genomes codify their own caspase inhibitory proteins, (14,20) such as viral-FLIPs (vFLIPs), protozoan parasites, instead, defray host cell apoptotic machinery (21) or exploit mammalian inhibitory proteins (22) to prevent cell death ( Figure 1a).…”

“…High rates of apoptosis may overcome the expansion and differentiation of lymphocytes, causing defective immune responses that allow parasite persistence ( Figure 1c). (16,19,62) T cells from hosts infected with T. cruzi, (63)(64)(65) T. gondii, (66)(67)(68) Plasmodium, (69)(70)(71) and Leishmania (72)(73)(74) show defective proliferation, cytokine or immune responses, associated with increased T cells apoptosis.…”