ArticlePLoS pathogens2020
Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
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- The early human interferon gamma response to Toxoplasma gondii is driven by Vγ9Vδ2 T-cell sensing of host phosphoantigens and subsequent NK-cell activation.PLoS pathogens · 2025Article
- Pleiotropic Effects on Tachyzoite and Host Cell Proteomes in Knock-Out Clones of the Open Reading Frames 297720 and 319730 Constitutively Expressed inInternational journal of molecular sciences · 2025Article
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- TIMP1 secretion induced bymSphere · 2025Article
- Discovery of host genetic factors through multi-locus GWAS against toxoplasmosis in sheep: addressing one health perspectives.BMC veterinary research · 2025Article
- Influence of MyD88 and αβ T cells on mesenteric lymph node innate lymphoid cell populations during Toxoplasma gondii infection.PloS one · 2025Article
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- Toll-like receptors in health and disease.MedComm · 2024Review
- Genome-wide and targeted CRISPR screens identify RNF213 as a mediator of interferon gamma-dependent pathogen restriction in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Capers with caspases: Toxoplasma gondii tales of inflammation and survival.Current opinion in microbiology · 2023Review
- The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages.Cell host & microbe · 2022Article
- Impact of MyD88, Microbiota, and Location on Type 1 and Type 3 Innate Lymphoid Cells duringImmunoHorizons · 2022Article
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- Anti-infection roles of miR-155-5p packaged in exosomes secreted by dendritic cells infected with Toxoplasma gondii.Parasites & vectors · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The murine innate immune response against Toxoplasma gondii is predominated by the interaction of TLR11/12 with Toxoplasma profilin. However, mice lacking Tlr11 or humans, who do not have functional TLR11 or TLR12, still elicit a strong innate immune response upon Toxoplasma infection. The parasite factors that determine this immune response are largely unknown. Herein, we investigated two dense granule proteins (GRAs) secreted by Toxoplasma, GRA15 and GRA24, for their role in stimulating the innate immune response in Tlr11-/- mice and in human cells, which naturally lack TLR11/TLR12. Our results show that GRA15 and GRA24 synergistically shape the early immune response and parasite virulence in Tlr11-/- mice, with GRA15 as the predominant effector. Nevertheless, acute virulence in Tlr11-/- mice is still dominated by allelic combinations of ROP18 and ROP5, which are effectors that determine evasion of the immunity-related GTPases. In human macrophages, GRA15 and GRA24 play a major role in the induction of IL12, IL18 and IL1β secretion. We further show that GRA15/GRA24-mediated IL12, IL18 and IL1β secretion activates IFNγ secretion by peripheral blood mononuclear cells (PBMCs), which controls Toxoplasma proliferation. Taken together, our study demonstrates the important role of GRA15 and GRA24 in activating the innate immune response in hosts lacking TLR11.
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