PXD003217

PXD003217 is an original dataset announced via ProteomeXchange.

Title	TRIM21 innate immune detection of GBP1-positive Toxoplasma gondii is essential for host survival
Description	Interferon 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:26:43.717.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vesela Encheva
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Toxoplasma gondii ME49; NCBI TaxID: 508771;
ModificationList	ubiquitinylated lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-11-20 00:30:58	ID requested
1	2018-03-12 02:14:31	announced
⏵ 2	2024-10-22 04:26:45	announced	2024-10-22: Updated project metadata.

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]

curator keyword: Biological, Biomedical

submitter keyword: proteomics,Toxoplasma gondii, TRIM21

Bram Snijders
contact affiliation	Crick Mass Spectrometry STP
contact email	Bram.Snijders@crick.ac.uk
lab head
Vesela Encheva
contact affiliation	The Francis Crick Institute
contact email	Vesela.Encheva@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003217
     1. Label: PRIDE project
     2. Name: TRIM21 innate immune detection of GBP1-positive Toxoplasma gondii is essential for host survival