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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 01, 2013 |
| Title |
A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite that resides inside a parasitophorous vacuole. During infection, Toxoplasma actively remodels the transcriptome of its hosting cells with profound and coupled impact on the host immune response. We report that Toxoplasma secretes GRA24, a novel dense granule protein which traffics from the vacuole to the host cell nucleus. Once released into the host cell, GRA24 has the unique ability to trigger prolonged autophosphorylation and nuclear translocation of the host cell p38α MAP kinase. This noncanonical kinetics of p38α activation correlates with the up-regulation of the transcription factors Egr-1 and c-Fos and the correlated synthesis of key proinflammatory cytokines, including interleukin-12 and the chemokine MCP-1, both known to control early parasite replication in vivo. Remarkably, the GRA24-p38α complex is defined by peculiar structural features and uncovers a new regulatory signaling path distinct from the MAPK signaling cascade and otherwise commonly activated by stress-related stimuli or various intracellular microbes.
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| Overall design |
GRA24 = PSP7
Mouse bone marrow-derived macrophages (BMDM) were infected with the following Toxoplasma gondii strains:
- RHku80 WT versus RHku80(deltaPSP7) mutant
- Pruku80 WT versus Pruku80(deltaPSP7) mutant
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| Contributor(s) |
Braun L, Brenier-Pinchart M, Yogavel M, Curt-Varesano A, Curt-Bertini R, Hussain T, Kieffer S, Coute Y, Pelloux H, Tardieux I, Sharma A, Belrhali H, Bougdour A, Hakimi MA |
| Citation(s) |
24043761 |
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| Submission date |
Jun 18, 2012 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Mohamed-ali HAKIMI |
| E-mail(s) |
[email protected]
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| Phone |
(33)476637469
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| Organization name |
CNRS
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| Department |
UMR5309
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| Lab |
IAB - HAKIMI Team
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| Street address |
Domaine de la Merci, Campus Santé
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| City |
LA TRONCHE |
| State/province |
Grenoble |
| ZIP/Postal code |
38700 |
| Country |
France |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (4)
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| GSM946935 |
PSP7-dependent host transcriptional responses in mouse BMDM infected with T. gondii [RH_PSP7-KO] |
| GSM946936 |
PSP7-dependent host transcriptional responses in mouse BMDM infected with T. gondii [Pru_PSP7-KO] |
| GSM949319 |
Host transcriptional responses in mouse BMDM infected with T. gondii [Pru_WT] |
| GSM949320 |
Host transcriptional responses in mouse BMDM infected with T. gondii [RH_WT] |
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| Relations |
| BioProject |
PRJNA168972 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38782_RAW.tar |
25.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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