ArticlePLoS biology2023
A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 51 citations in OpenAlex.
- Surface antigen SAG1 mediatesInfection and immunity · 2025Article
- From pathogen to cure: exploring the antitumor potential of Toxoplasma gondii.Infectious agents and cancer · 2025Review
- GRA12 is a common virulence factor across Toxoplasma gondii strains and mouse subspecies.Nature communications · 2025Article
- Paracrine rescue of MYR1-deficienteLife · 2024Article
- CRISPR screens identify genes essential formBio · 2024Article
- SPARK regulates AGC kinases central to theeLife · 2024Article
- SPARK regulates AGC kinases central to thebioRxiv : the preprint server for biology · 2024Article
- Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness.Parasites & vectors · 2024Article
- The role of IFN-γ-mediated host immune responses in monitoring and the elimination of Toxoplasma gondii infection.International immunology · 2024Review
- Host E3 ubiquitin ligase ITCH mediatesmBio · 2024Article
- Early immune response toFrontiers in cellular and infection microbiology · 2024Article
- IFNs in host defence and parasite immune evasion duringFrontiers in immunology · 2024Review
- A Combination of Four Nuclear Targeted Effectors ProtectsbioRxiv : the preprint server for biology · 2023Article
- Host E3 ubiquitin ligase ITCH mediatesbioRxiv : the preprint server for biology · 2023Article
- High-throughput identification of Toxoplasma gondii effector proteins that target host cell transcription.Cell host & microbe · 2023Article
- Genome-wide CRISPR screen identifies genes synthetically lethal with GRA17, a nutrient channel encoding gene in Toxoplasma.PLoS pathogens · 2023Article
- CRISPR Screens IdentifymBio · 2023Article
- Variation in CD8 T cell IFNγ differentiation to strains ofFrontiers in cellular and infection microbiology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Toxoplasma gondii secretes protein effectors to subvert the human immune system sufficiently to establish a chronic infection. Relative to murine infections, little is known about which parasite effectors disarm human immune responses. Here, we used targeted CRISPR screening to identify secreted protein effectors required for parasite survival in IFNγ-activated human cells. Independent screens were carried out using 2 Toxoplasma strains that differ in virulence in mice, leading to the identification of effectors required for survival in IFNγ-activated human cells. We identify the secreted protein GRA57 and 2 other proteins, GRA70 and GRA71, that together form a complex which enhances the ability of parasites to persist in IFNγ-activated human foreskin fibroblasts (HFFs). Components of the protein machinery required for export of Toxoplasma proteins into the host cell were also found to be important for parasite resistance to IFNγ in human cells, but these export components function independently of the identified protein complex. Host-mediated ubiquitination of the parasite vacuole has previously been associated with increased parasite clearance from human cells, but we find that vacuoles from GRA57, GRA70, and GRA71 knockout strains are surprisingly less ubiquitinated by the host cell. We hypothesise that this is likely a secondary consequence of deletion of the complex, unlinked to the IFNγ resistance mediated by these effectors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.