Dataset Information

TRIM21 innate immune detection of GBP1-positive Toxoplasma gondii is essential for host survival

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Toxoplasma Gondii Me49 Mus Musculus (mouse)

TISSUE(S): Fibroblast

SUBMITTER: Vesela Encheva

LAB HEAD: Bram Snijders

PROVIDER: PXD003217 | Pride | 2018-03-12

REPOSITORIES: Pride

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			Action	DRS
	PAF6779A10RW2_CFXB1PAF6779A10RW2-40-510456.raw	Raw
	PAF6779A11RW2_CFXC1PAF6779A11RW2-40-510433.raw	Raw
	PAF6779A12RW2_CFXD1PAF6779A12RW2-40-510434.raw	Raw
	PAF6779A13RW2_CFXE1PAF6779A13RW2-40-510436.raw	Raw
	PAF6779A14RW2_CFXF1PAF6779A14RW2-40-510437.raw	Raw

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Murine Gbp1 and Gbp2 are ubiquitinated independent of Toxoplasma gondii infection.

Encheva Vesela V Foltz Clémence C Snijders Ambrosius P AP Frickel Eva-Maria EM

BMC research notes 20180306 1

<h4>Objective</h4>The intracellular parasite Toxoplasma gondii can invade any nucleated cell residing inside a parasitophorous vacuole (PV). Upon infection, the cytokine interferon gamma (IFNγ) is produced and elicits host defence mechanisms able to recognise the PV and destroy the parasite. Hereby, Guanylate binding proteins, ubiquitin and the E3 ubiquitin ligases Tripartite Motif Containing 21 (TRIM21) and TNF receptor associated factor 6 are targeted to the murine PV leading to its destructio ...[more]

PMID: 29510761

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