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Toxoplasma Effectors Targeting Host Signaling and Transcription
Mohamed-Ali Hakimi1, Philipp Olias2,3, L David Sibley4
1Institute for Advanced Biosciences, Team Host-Pathogen Interactions and Immunity to Infection, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.
Clinical Microbiology Reviews
|April 14, 2017
Summary
Toxoplasma gondii parasites use specialized secretory organelles, rhoptry (ROP) and dense granules (GRAs), to manipulate host cells. These parasite effectors target host signaling pathways, aiding intracellular survival.
Area of Science:
- Parasitology
- Cell Biology
- Molecular Biology
Background:
- Apicomplexan parasites possess unique cellular structures like rhoptry (ROP) and dense granule (GRA) organelles.
- These organelles secrete diverse proteins during host cell invasion, impacting host-pathogen interactions.
- Early studies identified altered host signaling pathways but lacked direct links to parasite effectors.
Purpose of the Study:
- To elucidate the functions of parasite-secreted proteins from ROP and GRA organelles.
- To connect specific parasite effectors to the host signaling pathways they modulate.
- To understand how these effectors facilitate intracellular survival of *Toxoplasma gondii*.
Main Methods:
- Utilized forward and reverse genetic strategies to identify effector functions.
- Investigated the molecular mechanisms by which ROP and GRA proteins interact with host cells.
- Analyzed the impact of effector proteins on host gene expression and immune responses.
Main Results:
- ROP kinases and pseudokinases block host immune pathways upon secretion during invasion.
- GRA proteins modify host gene expression via transcription factors, chromatin, or small noncoding RNAs.
- Identified novel mechanisms of host signaling manipulation by *T. gondii*.
Conclusions:
- *Toxoplasma gondii* employs a sophisticated arsenal of secreted effectors to hijack host cell machinery.
- These effectors are crucial for parasite survival and persistence within the host.
- Further research will uncover the intricate complexity of this host-pathogen interaction.