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Series GSE38782 Query DataSets for GSE38782
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
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.
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
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
Submission date Jun 18, 2012
Last update date Nov 01, 2017
Contact name Mohamed-ali HAKIMI
Phone (33)476637469
Organization name CNRS
Department UMR5309
Street address Domaine de la Merci, Campus Santé
State/province Grenoble
ZIP/Postal code 38700
Country France
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (4)
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]
BioProject PRJNA168972

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Series Matrix File(s) TXTHelp

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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