Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection

ABSTRACT 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...

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Autores principales: Nora Steffens, Cornelia Beuter-Gunia, Elisabeth Kravets, Artur Reich, Larissa Legewie, Klaus Pfeffer, Daniel Degrandi
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:e6c6e2bef0924ad18452538863dcdfd62021-11-15T15:56:57ZEssential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection10.1128/mBio.02993-192150-7511https://doaj.org/article/e6c6e2bef0924ad18452538863dcdfd62020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02993-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Guanylate-binding proteins (GBPs) are induced by the inflammatory cytokine interferon gamma (IFN-γ) and have been shown to be important factors in the defense of the intracellular pathogen Toxoplasma gondii. In previous studies, we showed that members of the mouse GBP family, such as mGBP2 and mGBP7, accumulate at the parasitophorous vacuole of T. gondii, which is the replicatory niche of the parasite. In this study, we show that mice deficient in mGBP7 succumb early after infection with T. gondii, showing a complete failure of resistance to the pathogen. On a molecular level, mGBP7 is found directly at the parasite, likely mediating its destruction.Nora SteffensCornelia Beuter-GuniaElisabeth KravetsArtur ReichLarissa LegewieKlaus PfefferDaniel DegrandiAmerican Society for Microbiologyarticleguanylate-binding proteinscell-autonomous immunityToxoplasma gondiihost-pathogen interactioninterferonsmGBP7MicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution DOAJ
collection DOAJ
language EN
topic guanylate-binding proteins
cell-autonomous immunity
Toxoplasma gondii
host-pathogen interaction
interferons
mGBP7
Microbiology
QR1-502
spellingShingle guanylate-binding proteins
cell-autonomous immunity
Toxoplasma gondii
host-pathogen interaction
interferons
mGBP7
Microbiology
QR1-502
Nora Steffens
Cornelia Beuter-Gunia
Elisabeth Kravets
Artur Reich
Larissa Legewie
Klaus Pfeffer
Daniel Degrandi
Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection
description ABSTRACT 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. IMPORTANCE Guanylate-binding proteins (GBPs) are induced by the inflammatory cytokine interferon gamma (IFN-γ) and have been shown to be important factors in the defense of the intracellular pathogen Toxoplasma gondii. In previous studies, we showed that members of the mouse GBP family, such as mGBP2 and mGBP7, accumulate at the parasitophorous vacuole of T. gondii, which is the replicatory niche of the parasite. In this study, we show that mice deficient in mGBP7 succumb early after infection with T. gondii, showing a complete failure of resistance to the pathogen. On a molecular level, mGBP7 is found directly at the parasite, likely mediating its destruction.
format article
author Nora Steffens
Cornelia Beuter-Gunia
Elisabeth Kravets
Artur Reich
Larissa Legewie
Klaus Pfeffer
Daniel Degrandi
author_facet Nora Steffens
Cornelia Beuter-Gunia
Elisabeth Kravets
Artur Reich
Larissa Legewie
Klaus Pfeffer
Daniel Degrandi
author_sort Nora Steffens
title Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection
title_short Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection
title_full Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection
title_fullStr Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection
title_full_unstemmed Essential Role of mGBP7 for Survival of <named-content content-type="genus-species">Toxoplasma gondii</named-content> Infection
title_sort essential role of mgbp7 for survival of <named-content content-type="genus-species">toxoplasma gondii</named-content> infection
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/e6c6e2bef0924ad18452538863dcdfd6
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