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Inhibition of apoptosis by intracellular protozoan parasites
V T Heussler1, P Küenzi, S Rottenberg
1Molecular Pathology, Institute of Animal Pathology, University of Berne, Switzerland. volker.heussler@itpa.unibe.ch
Abstract:
Protozoan parasites which reside inside a host cell avoid direct destruction by the immune system of the host. The infected cell, however, still has the capacity to counteract the invasive pathogen by initiating its own death, a process which is called programmed cell death or apoptosis. Apoptotic cells are recognised and phagocytosed by macrophages and the parasite is potentially eliminated together with the infected cell. This potent defence mechanism of the host cell puts strong selective pressure on the parasites which have, in turn, evolved strategies to modulate the apoptotic program of the host cell to their favour. Within the last decade, the existence of cellular signalling pathways which inhibit the apoptotic machinery has been demonstrated. It is not surprising that intracellular pathogens subvert these pathways to ensure their own survival in the infected cell. Molecular mechanisms which interfere with apoptotic pathways have been studied extensively for viruses and parasitic bacteria, but protozoan parasites have come into focus only recently. Intracellular protozoan parasites which have been reported to inhibit the apoptotic program of the host cell, are Toxoplasma gondii, Trypanosoma cruzi, Leishmania sp., Theileria sp., Cryptosporidium parvum, and the microsporidian Nosema algerae. Although these parasites differ in their mechanism of host cell entry and in their final intracellular localisation, they might activate similar pathways in their host cells to inhibit apoptosis. In this respect, two families of molecules, which are known for their capacity to interrupt the apoptotic program, are currently discussed in the literature. First, the expression of heat shock proteins is often induced upon parasite infection and can directly interfere with molecules of the cellular death machinery. Secondly, a more indirect effect is attributed to the parasite-dependent activation of NF-kappaB, a transcription factor that regulates the transcription of anti-apoptotic molecules.
Insights
Intracellular protozoan parasites evade host immunity by inhibiting programmed cell death (apoptosis). They manipulate host cell pathways, often using heat shock proteins or NF-kappaB activation, to survive and replicate within infected cells.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Intracellular protozoan parasites infect host cells, evading direct immune attack.
- Host cells possess a defense mechanism called programmed cell death (apoptosis) to eliminate infected cells.
- Parasites have evolved strategies to subvert host apoptosis for their survival.
Purpose of the Study:
- To review the mechanisms by which intracellular protozoan parasites inhibit host cell apoptosis.
- To highlight the recent focus on protozoan parasites' manipulation of apoptotic pathways.
Main Methods:
- Literature review of studies on protozoan parasites and apoptosis.
- Analysis of molecular mechanisms employed by parasites to interfere with host cell death pathways.
Main Results:
- Several protozoan parasites, including Toxoplasma gondii and Leishmania sp., are known to inhibit host apoptosis.
- Parasites may utilize heat shock proteins and NF-kappaB activation to suppress the apoptotic machinery.
- These mechanisms allow parasites to ensure their survival within the host cell.
Conclusions:
- Intracellular protozoan parasites actively manipulate host cell apoptosis to ensure their survival.
- Understanding these parasite-driven apoptotic inhibition pathways is crucial for developing new therapeutic strategies.