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Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection

Members of the murine guanylate-binding protein family (mGBP) are induced by interferon gamma (IFN-γ) and have been shown to be important factors in cell-autonomous immunity toward the intracellular pathogen Toxoplasma gondii. Previously, we identified that mGBP2 mediates disruption of the parasitop...

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Autores principales: Steffens, Nora, Beuter-Gunia, Cornelia, Kravets, Elisabeth, Reich, Artur, Legewie, Larissa, Pfeffer, Klaus, Degrandi, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974569/
https://www.ncbi.nlm.nih.gov/pubmed/31964735
http://dx.doi.org/10.1128/mBio.02993-19
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author Steffens, Nora
Beuter-Gunia, Cornelia
Kravets, Elisabeth
Reich, Artur
Legewie, Larissa
Pfeffer, Klaus
Degrandi, Daniel
author_facet Steffens, Nora
Beuter-Gunia, Cornelia
Kravets, Elisabeth
Reich, Artur
Legewie, Larissa
Pfeffer, Klaus
Degrandi, Daniel
author_sort Steffens, Nora
collection PubMed
description Members of the murine guanylate-binding protein family (mGBP) are induced by interferon gamma (IFN-γ) and have been shown to be important factors in cell-autonomous immunity toward the intracellular pathogen Toxoplasma gondii. Previously, we identified that mGBP2 mediates disruption of the parasitophorous vacuole membrane (PVM) and directly assaults the plasma membrane of the parasite. Here, we show that mGBP7-deficient mice are highly susceptible to T. gondii infection. This is demonstrated by the loss of parasite replication control, pronounced development of ascites, and death of the animals in the acute infection phase. Interestingly, live-cell microscopy revealed that mGBP7 recruitment to the PVM occurs after mGBP2 recruitment, followed by disruption of the PVM and T. gondii integrity and accumulation of mGBP7 inside the parasite. This study defines mGBP7 as a crucial effector protein in resistance to intracellular T. gondii.
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spelling pubmed-69745692020-02-04 Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection Steffens, Nora Beuter-Gunia, Cornelia Kravets, Elisabeth Reich, Artur Legewie, Larissa Pfeffer, Klaus Degrandi, Daniel mBio Research Article Members of the murine guanylate-binding protein family (mGBP) are induced by interferon gamma (IFN-γ) and have been shown to be important factors in cell-autonomous immunity toward the intracellular pathogen Toxoplasma gondii. Previously, we identified that mGBP2 mediates disruption of the parasitophorous vacuole membrane (PVM) and directly assaults the plasma membrane of the parasite. Here, we show that mGBP7-deficient mice are highly susceptible to T. gondii infection. This is demonstrated by the loss of parasite replication control, pronounced development of ascites, and death of the animals in the acute infection phase. Interestingly, live-cell microscopy revealed that mGBP7 recruitment to the PVM occurs after mGBP2 recruitment, followed by disruption of the PVM and T. gondii integrity and accumulation of mGBP7 inside the parasite. This study defines mGBP7 as a crucial effector protein in resistance to intracellular T. gondii. American Society for Microbiology 2020-01-21 /pmc/articles/PMC6974569/ /pubmed/31964735 http://dx.doi.org/10.1128/mBio.02993-19 Text en Copyright © 2020 Steffens et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Steffens, Nora
Beuter-Gunia, Cornelia
Kravets, Elisabeth
Reich, Artur
Legewie, Larissa
Pfeffer, Klaus
Degrandi, Daniel
Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection
title Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection
title_full Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection
title_fullStr Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection
title_full_unstemmed Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection
title_short Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection
title_sort essential role of mgbp7 for survival of toxoplasma gondii infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974569/
https://www.ncbi.nlm.nih.gov/pubmed/31964735
http://dx.doi.org/10.1128/mBio.02993-19
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