ArticlePLoS pathogens2020
Toxoplasma gondii dense granule protein GRA24 drives MyD88-independent p38 MAPK activation, IL-12 production and induction of protective immunity.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Toxoplasma gondii as a drug for anti-tumor immunotherapy: mechanisms, challenges, and perspectives.Parasite (Paris, France) · 2026Review
- Influence of MyD88 and αβ T cells on mesenteric lymph node innate lymphoid cell populations during Toxoplasma gondii infection.PloS one · 2025Article
- Article
- iNOS is necessary for GBP-mediated T. gondii clearance in murine macrophages via vacuole nitration and intravacuolar network collapse.Nature communications · 2024Article
- Article
- Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection.Parasites & vectors · 2023Review
- Article
- The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages.Cell host & microbe · 2022Article
- DGPD: a knowledge database of dense granule proteins of the Apicomplexa.Database : the journal of biological databases and curation · 2022Article
- Impact of MyD88, Microbiota, and Location on Type 1 and Type 3 Innate Lymphoid Cells duringImmunoHorizons · 2022Article
- Intestinal immune responses to commensal and pathogenic protozoa.Frontiers in immunology · 2022Review
- TLR7 modulating B-cell immune responses in the spleen of C57BL/6 mice infected with Schistosoma japonicum.PLoS neglected tropical diseases · 2021Article
- Synergy betweenJournal for immunotherapy of cancer · 2021Article
- Lessons from Toxoplasma: Host responses that mediate parasite control and the microbial effectors that subvert them.The Journal of experimental medicine · 2021Review
- Induction of IL-12p40 and type 1 immunity by Toxoplasma gondii in the absence of the TLR-MyD88 signaling cascade.PLoS pathogens · 2021Article
- Secreted Effectors Modulating Immune Responses toLife (Basel, Switzerland) · 2021Review
- Toxoplasma gondii infection and its implications within the central nervous system.Nature reviews. Microbiology · 2021Review
- IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity toeLife · 2021Article
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The apicomplexan Toxoplasma gondii induces strong protective immunity dependent upon recognition by Toll-like receptors (TLR)11 and 12 operating in conjunction with MyD88 in the murine host. However, TLR11 and 12 proteins are not present in humans, inspiring us to investigate MyD88-independent pathways of resistance. Using bicistronic IL-12-YFP reporter mice on MyD88+/+ and MyD88-/- genetic backgrounds, we show that CD11c+MHCII+F4/80- dendritic cells, F4/80+ macrophages, and Ly6G+ neutrophils were the dominant cellular sources of IL-12 in both wild type and MyD88 deficient mice after parasite challenge. Parasite dense granule protein GRA24 induces p38 MAPK activation and subsequent IL-12 production in host macrophages. We show that Toxoplasma triggers an early and late p38 MAPK phosphorylation response in MyD88+/+ and MyD88-/- bone marrow-derived macrophages. Using the uracil auxotrophic Type I T. gondii strain cps1-1, we demonstrate that the late response does not require active parasite proliferation, but strictly depends upon GRA24. By i. p. inoculation with cps1-1 and cps1-1:Δgra24, we identified unique subsets of chemokines and cytokines that were up and downregulated by GRA24. Finally, we demonstrate that cps1-1 triggers a strong host-protective GRA24-dependent Th1 response in the absence of MyD88. Our data identify GRA24 as a major mediator of p38 MAPK activation, IL-12 induction and protective immunity that operates independently of the TLR/MyD88 cascade.
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Registered trials
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.