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Published on: March 16, 2018
Mechanisms regulating host cell death during Leishmania infection
Juliane C R Fernandes1, Dario S Zamboni1
1Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Abstract:
Parasites from the Leishmania genus are the causative agents of leishmaniasis and primarily reside within macrophages during mammalian infection. Their ability to establish intracellular infection provides a secure niche for proliferation while evading detection. However, successful multiplication within mammalian cells requires the orchestration of multiple mechanisms that control host cell viability. In contrast, innate immune cells, such as macrophages, can undergo different forms of cell death in response to pathogenic intracellular microbes. Thus, modulation of these different forms of host cell death is crucial for Leishmaniasis development. The regulation of host cell apoptosis, a form of programmed cell death, is crucial for sustaining parasites within viable host cells. Accordingly, several studies have demonstrated evasion of apoptosis induced by dermotropic and viscerotropic Leishmania species. Conversely, the prevention of pyroptosis, an inflammatory form of cell death, ensures the establishment of infection by silencing the release of mediators that could trigger massive proinflammatory responses. This manuscript explores how Leishmania regulates various host cell death pathways and overviews seminal studies on regulating host cell apoptosis by different Leishmania species.
Insights
Leishmania parasites manipulate host cell death, evading apoptosis for survival and preventing pyroptosis to establish infection. Understanding these parasite-host interactions is key to controlling leishmaniasis.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Leishmania parasites cause leishmaniasis, residing within host macrophages.
- Intracellular survival necessitates control over host cell viability mechanisms.
- Host cell death pathways are critical battlegrounds in Leishmania infections.
Purpose of the Study:
- To explore how Leishmania parasites regulate host cell death pathways.
- To review studies on Leishmania's modulation of apoptosis and pyroptosis.
- To understand parasite strategies for intracellular proliferation and immune evasion.
Main Methods:
- Literature review of existing studies on Leishmania and host cell death.
- Analysis of parasite-induced apoptosis evasion mechanisms.
- Investigation of parasite-mediated pyroptosis inhibition.
Main Results:
- Leishmania species evade host cell apoptosis, ensuring parasite survival within viable macrophages.
- Parasites prevent pyroptosis, a pro-inflammatory cell death, to limit immune responses.
- Differential regulation of cell death pathways is crucial for Leishmania pathogenesis.
Conclusions:
- Leishmania actively manipulates host cell death pathways for successful infection.
- Targeting these host-parasite interactions could offer new therapeutic strategies for leishmaniasis.
- Further research into parasite-controlled cell death is vital for understanding and treating leishmaniasis.
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