mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.

Guanylate binding proteins (GBPs) are large interferon-inducible GTPases, executing essential host defense activities against Toxoplasma gondii, an invasive intracellular apicomplexan protozoan parasite of global importance. T. gondii establishes a parasitophorous vacuole (PV) which shields the para...

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Main Authors: Elisabeth Kravets, Gereon Poschmann, Sebastian Hänsch, Veronica Raba, Stefanie Weidtkamp-Peters, Daniel Degrandi, Kai Stühler, Klaus Pfeffer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0316209
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author Elisabeth Kravets
Gereon Poschmann
Sebastian Hänsch
Veronica Raba
Stefanie Weidtkamp-Peters
Daniel Degrandi
Kai Stühler
Klaus Pfeffer
author_facet Elisabeth Kravets
Gereon Poschmann
Sebastian Hänsch
Veronica Raba
Stefanie Weidtkamp-Peters
Daniel Degrandi
Kai Stühler
Klaus Pfeffer
author_sort Elisabeth Kravets
collection DOAJ
description Guanylate binding proteins (GBPs) are large interferon-inducible GTPases, executing essential host defense activities against Toxoplasma gondii, an invasive intracellular apicomplexan protozoan parasite of global importance. T. gondii establishes a parasitophorous vacuole (PV) which shields the parasite from the host's intracellular defense mechanisms. Murine GBPs (mGBPs) recognize T. gondii PVs and assemble into supramolecular mGBP homo- and heterocomplexes that are required for the disruption of the membrane of PVs eventually resulting in the cell-autonomous immune control of vacuole-resident pathogens. We have previously shown that mGBP2 plays an important role in T. gondii immune control. Here, to unravel mGBP2 functions, we report Galectin-9 (Gal9) as a critical mGBP2 interaction partner engaged for immunity to T. gondii. Interestingly, Gal9 also accumulates and colocalizes with mGBP2 at the T. gondii PV. Furthermore, we could prove the requirement of Gal9 for growth control of T. gondii by CRISPR/Cas9 mediated gene editing. These discoveries clearly indicate that Gal9 is a crucial factor for the mGBP2-coordinated cell-autonomous host defense mechanism against T. gondii.
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spelling doaj-art-06085beb1b0041d2b6de8896c09c793a2025-02-01T05:30:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031620910.1371/journal.pone.0316209mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.Elisabeth KravetsGereon PoschmannSebastian HänschVeronica RabaStefanie Weidtkamp-PetersDaniel DegrandiKai StühlerKlaus PfefferGuanylate binding proteins (GBPs) are large interferon-inducible GTPases, executing essential host defense activities against Toxoplasma gondii, an invasive intracellular apicomplexan protozoan parasite of global importance. T. gondii establishes a parasitophorous vacuole (PV) which shields the parasite from the host's intracellular defense mechanisms. Murine GBPs (mGBPs) recognize T. gondii PVs and assemble into supramolecular mGBP homo- and heterocomplexes that are required for the disruption of the membrane of PVs eventually resulting in the cell-autonomous immune control of vacuole-resident pathogens. We have previously shown that mGBP2 plays an important role in T. gondii immune control. Here, to unravel mGBP2 functions, we report Galectin-9 (Gal9) as a critical mGBP2 interaction partner engaged for immunity to T. gondii. Interestingly, Gal9 also accumulates and colocalizes with mGBP2 at the T. gondii PV. Furthermore, we could prove the requirement of Gal9 for growth control of T. gondii by CRISPR/Cas9 mediated gene editing. These discoveries clearly indicate that Gal9 is a crucial factor for the mGBP2-coordinated cell-autonomous host defense mechanism against T. gondii.https://doi.org/10.1371/journal.pone.0316209
spellingShingle Elisabeth Kravets
Gereon Poschmann
Sebastian Hänsch
Veronica Raba
Stefanie Weidtkamp-Peters
Daniel Degrandi
Kai Stühler
Klaus Pfeffer
mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.
PLoS ONE
title mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.
title_full mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.
title_fullStr mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.
title_full_unstemmed mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.
title_short mGBP2 engages Galectin-9 for immunity against Toxoplasma gondii.
title_sort mgbp2 engages galectin 9 for immunity against toxoplasma gondii
url https://doi.org/10.1371/journal.pone.0316209
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