TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles

Abstract Interferon gamma (IFNγ) is the major proinflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii by inducing the destruction of the parasitophorous vacuole (PV). We previously identified TRIM21 as an IFNγ-driven E3 ubiquitin ligase mediating the d...

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Autores principales:	Clémence Foltz, Anna Napolitano, Rabia Khan, Barbara Clough, Elizabeth M. Hirst, Eva-Maria Frickel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/166b4c5cdada44f58f4e8b6bf0980473
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spelling	oai:doaj.org-article:166b4c5cdada44f58f4e8b6bf09804732021-12-02T11:52:56ZTRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles10.1038/s41598-017-05487-72045-2322https://doaj.org/article/166b4c5cdada44f58f4e8b6bf09804732017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05487-7https://doaj.org/toc/2045-2322Abstract Interferon gamma (IFNγ) is the major proinflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii by inducing the destruction of the parasitophorous vacuole (PV). We previously identified TRIM21 as an IFNγ-driven E3 ubiquitin ligase mediating the deposition of ubiquitin around pathogen inclusions. Here, we show that TRIM21 knockout mice were highly susceptible to Toxoplasma infection, exhibiting decreased levels of serum inflammatory cytokines and higher parasite burden in the peritoneum and brain. We demonstrate that IFNγ drives recruitment of TRIM21 to GBP1-positive Toxoplasma vacuoles, leading to Lys63-linked ubiquitination of the vacuole and restriction of parasite early replication without interfering with vacuolar disruption. As seen in vivo, TRIM21 impacted the secretion of inflammatory cytokines. This study identifies TRIM21 as a previously unknown modulator of Toxoplasma gondii resistance in vivo thereby extending host innate immune recognition of eukaryotic pathogens to include E3 ubiquitin ligases.Clémence FoltzAnna NapolitanoRabia KhanBarbara CloughElizabeth M. HirstEva-Maria FrickelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Clémence Foltz Anna Napolitano Rabia Khan Barbara Clough Elizabeth M. Hirst Eva-Maria Frickel TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles
description	Abstract Interferon gamma (IFNγ) is the major proinflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii by inducing the destruction of the parasitophorous vacuole (PV). We previously identified TRIM21 as an IFNγ-driven E3 ubiquitin ligase mediating the deposition of ubiquitin around pathogen inclusions. Here, we show that TRIM21 knockout mice were highly susceptible to Toxoplasma infection, exhibiting decreased levels of serum inflammatory cytokines and higher parasite burden in the peritoneum and brain. We demonstrate that IFNγ drives recruitment of TRIM21 to GBP1-positive Toxoplasma vacuoles, leading to Lys63-linked ubiquitination of the vacuole and restriction of parasite early replication without interfering with vacuolar disruption. As seen in vivo, TRIM21 impacted the secretion of inflammatory cytokines. This study identifies TRIM21 as a previously unknown modulator of Toxoplasma gondii resistance in vivo thereby extending host innate immune recognition of eukaryotic pathogens to include E3 ubiquitin ligases.
format	article
author	Clémence Foltz Anna Napolitano Rabia Khan Barbara Clough Elizabeth M. Hirst Eva-Maria Frickel
author_facet	Clémence Foltz Anna Napolitano Rabia Khan Barbara Clough Elizabeth M. Hirst Eva-Maria Frickel
author_sort	Clémence Foltz
title	TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles
title_short	TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles
title_full	TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles
title_fullStr	TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles
title_full_unstemmed	TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles
title_sort	trim21 is critical for survival of toxoplasma gondii infection and localises to gbp-positive parasite vacuoles
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/166b4c5cdada44f58f4e8b6bf0980473
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TRIM21 is critical for survival of Toxoplasma gondii infection and localises to GBP-positive parasite vacuoles

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