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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American Society for Microbiology
2020
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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) |
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guanylate-binding proteins cell-autonomous immunity Toxoplasma gondii host-pathogen interaction interferons mGBP7 Microbiology QR1-502 |
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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 |
work_keys_str_mv |
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