ArticleThe Journal of experimental medicine2014
Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- The imbalance in the relationship between inflammatory and regulatory cytokines during gestational toxoplasmosis can be harmful to fetuses: A systematic review.Frontiers in immunology · 2023Pooled it
- GRA86 Is a Novel Dense Granule Protein Important for Virulence and Bradyzoite Differentiation inAnimals : an open access journal from MDPI · 2025Article
- Human Retinal Organoid Model of Ocular Toxoplasmosis.Pathogens (Basel, Switzerland) · 2025Article
- Study of dense granule proteins inFrontiers in immunology · 2025Article
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- Toxoplasma gondii-Derived Exosomes: A Potential Immunostimulant and Delivery System for Tumor Immunotherapy Superior to Toxoplasma gondii.International journal of nanomedicine · 2024Review
- Toxoplasma protein export and effector function.Nature microbiology · 2024Review
- Toxoplasma-host endoplasmic reticulum interaction: HowCurrent research in microbial sciences · 2024Review
- Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection.Parasites & vectors · 2023Review
- 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
- Functional Characterization of 15 Novel Dense Granule Proteins in Toxoplasma gondii Using the CRISPR-Cas9 System.Microbiology spectrum · 2023Article
- Overview of Apoptosis, Autophagy, and Inflammatory Processes inPathogens (Basel, Switzerland) · 2023Review
- The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages.Cell host & microbe · 2022Article
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- Single Cell Transcriptomes ofFrontiers in cellular and infection microbiology · 2022Article
- The pathogenicity and virulence ofVirulence · 2021Article
- Secreted Effectors Modulating Immune Responses toLife (Basel, Switzerland) · 2021Review
- Uncovering a novel role of PLCβ4 in selectively mediating TCR signaling in CD8+ but not CD4+ T cells.The Journal of experimental medicine · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxoplasma gondii infection results in co-option and subversion of host cellular signaling pathways. This process involves discharge of T. gondii effector molecules from parasite secretory organelles such as rhoptries and dense granules. We report that the T. gondii polymorphic dense granule protein GRA6 regulates activation of the host transcription factor nuclear factor of activated T cells 4 (NFAT4). GRA6 overexpression robustly and selectively activated NFAT4 via calcium modulating ligand (CAMLG). Infection with wild-type (WT) but not GRA6-deficient parasites induced NFAT4 activation. Moreover, GRA6-deficient parasites failed to exhibit full virulence in local infection, and the treatment of WT mice with an NFAT inhibitor mitigated virulence of WT parasites. Notably, NFAT4-deficient mice displayed prolonged survival, decreased recruitment of CD11b(+) Ly6G(+) cells to the site of infection, and impaired expression of chemokines such as Cxcl2 and Ccl2. In addition, infection with type I parasites culminated in significantly higher NFAT4 activation than type II parasites due to a polymorphism in the C terminus of GRA6. Collectively, our data suggest that GRA6-dependent NFAT4 activation is required for T. gondii manipulation of host immune responses to maximize the parasite virulence in a strain-dependent manner.
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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.