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PXD003217

PXD003217 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTRIM21 innate immune detection of GBP1-positive Toxoplasma gondii is essential for host survival
DescriptionInterferon gamma (IFN) is the major pro-inflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii. Autophagy along with immunity-related GTPases (IRGs), guanylate binding proteins (GBPs) and the E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) mediate clearance of Toxoplasma in IFN-stimulated cells. With the exception of inflammasomes, no host innate immune mediators impacting host survival have been identified at disrupted parasitophorous vacuoles. We show that IFN drives recruitment of the E3 ubiquitin ligase TRIM21 to GBP1-positive avirulent Toxoplasma vacuoles. This led to Lys63-linked ubiquitination of the vacuole and secretion of pro-inflammatory cytokines. GBPs were ubiquitinated during infection and TRIM21 controlled their expression levels and the efficient recruitment of GBP1 to the vacuole. TRIM21 deficiency led to an enhanced early replication of Toxoplasma without interfering with vacuolar disruption. TRIM21-/- mice were highly susceptible to Toxoplasma infection, exhibiting decreased levels of pro-inflammatory cytokines and higher parasite burden in the brain. This study identifies TRIM21 as a previously unknown modulator of Toxoplasma gondii resistance thereby extending host innate immune recognition of eukaryotic pathogens to include E3 ubiquitin ligases.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:26:43.717.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVesela Encheva
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Toxoplasma gondii ME49; NCBI TaxID: 508771;
ModificationListubiquitinylated lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-11-20 00:30:58ID requested
12018-03-12 02:14:31announced
22024-10-22 04:26:45announced2024-10-22: Updated project metadata.
Publication List
10.1186/s13104-018-3267-z;
Encheva V, Foltz C, Snijders AP, Frickel EM, Murine Gbp1 and Gbp2 are ubiquitinated independent of Toxoplasma gondii infection. BMC Res Notes, 11(1):166(2018) [pubmed]
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: proteomics,Toxoplasma gondii, TRIM21
Contact List
Bram Snijders
contact affiliationCrick Mass Spectrometry STP
contact emailBram.Snijders@crick.ac.uk
lab head
Vesela Encheva
contact affiliationThe Francis Crick Institute
contact emailVesela.Encheva@crick.ac.uk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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