ArticlePLoS pathogens2009
Disruption of the Toxoplasma gondii parasitophorous vacuole by IFNgamma-inducible immunity-related GTPases (IRG proteins) triggers necrotic cell death.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 2 of them syntheses that pooled it.
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149 citing papers in PubMed, 2 syntheses or guidelines pooled it, 227 citations in OpenAlex.
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- Functional characterization of 11 novel rhoptry proteins in the type I RH strain of Toxoplasma gondii using the CRISPR-Cas9 system.Parasites & vectors · 2026Article
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- Evaluation ofInfection and immunity · 2025Article
- The cat's out of the bag: Toxoplasma gondii provides further insight into myeloid-mediated host defense.ImmunoHorizons · 2025Review
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- GRA12 is a common virulence factor across Toxoplasma gondii strains and mouse subspecies.Nature communications · 2025Article
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- Type I interferon signaling and peroxisomal dysfunction contribute to enhanced inflammatory cytokine production in IRGM1-deficient macrophages.The Journal of biological chemistry · 2024Article
- Proteomic approaches for protein kinase substrate identification in Apicomplexa.Molecular and biochemical parasitology · 2024Review
- Effective factors in the pathogenesis ofHeliyon · 2024Review
- iNOS is necessary for GBP-mediated T. gondii clearance in murine macrophages via vacuole nitration and intravacuolar network collapse.Nature communications · 2024Article
- Host E3 ubiquitin ligase ITCH mediatesmBio · 2024Article
- IFNs in host defence and parasite immune evasion duringFrontiers in immunology · 2024Review
- Reduced neural progenitor cell count and cortical neurogenesis in guinea pigs congenitally infected with Toxoplasma gondii.Communications biology · 2023Article
- A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells.PLoS biology · 2023Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxoplasma gondii is a natural intracellular protozoal pathogen of mice and other small mammals. After infection, the parasite replicates freely in many cell types (tachyzoite stage) before undergoing a phase transition and encysting in brain and muscle (bradyzoite stage). In the mouse, early immune resistance to the tachyzoite stage is mediated by the family of interferon-inducible immunity-related GTPases (IRG proteins), but little is known of the nature of this resistance. We reported earlier that IRG proteins accumulate on intracellular vacuoles containing the pathogen, and that the vacuolar membrane subsequently ruptures. In this report, live-cell imaging microscopy has been used to follow this process and its consequences in real time. We show that the rupture of the vacuole is inevitably followed by death of the intracellular parasite, shown by its permeability to cytosolic protein markers. Death of the parasite is followed by the death of the infected cell. The death of the cell has features of pyronecrosis, including membrane permeabilisation and release of the inflammatory protein, HMGB1, but caspase-1 cleavage is not detected. This sequence of events occurs on a large scale only following infection of IFNgamma-induced cells with an avirulent strain of T. gondii, and is reduced by expression of a dominant negative mutant IRG protein. Cells infected by virulent strains rarely undergo necrosis. We did not find autophagy to play any role in the key steps leading to the death of the parasite. We conclude that IRG proteins resist infection by avirulent T. gondii by a novel mechanism involving disruption of the vacuolar membrane, which in turn ultimately leads to the necrotic death of the infected cell.
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