Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice

Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG pro...

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Autores principales: Murillo-León, Mateo, Müller, Urs B., Zimmermann, Ines, Singh, Shishir, Widdershooven, Pia, Campos, Cláudia, Alvarez, Catalina, Könen-Waisman, Stephanie, Lukes, Nahleen, Ruzsics, Zsolt, Howard, Jonathan C., Schwemmle, Martin, Steinfeldt, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420625/
https://www.ncbi.nlm.nih.gov/pubmed/30874554
http://dx.doi.org/10.1038/s41467-019-09200-2
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author Murillo-León, Mateo
Müller, Urs B.
Zimmermann, Ines
Singh, Shishir
Widdershooven, Pia
Campos, Cláudia
Alvarez, Catalina
Könen-Waisman, Stephanie
Lukes, Nahleen
Ruzsics, Zsolt
Howard, Jonathan C.
Schwemmle, Martin
Steinfeldt, Tobias
author_facet Murillo-León, Mateo
Müller, Urs B.
Zimmermann, Ines
Singh, Shishir
Widdershooven, Pia
Campos, Cláudia
Alvarez, Catalina
Könen-Waisman, Stephanie
Lukes, Nahleen
Ruzsics, Zsolt
Howard, Jonathan C.
Schwemmle, Martin
Steinfeldt, Tobias
author_sort Murillo-León, Mateo
collection PubMed
description Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1(CIM) to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1(CIM), indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors.
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spelling pubmed-64206252019-03-18 Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice Murillo-León, Mateo Müller, Urs B. Zimmermann, Ines Singh, Shishir Widdershooven, Pia Campos, Cláudia Alvarez, Catalina Könen-Waisman, Stephanie Lukes, Nahleen Ruzsics, Zsolt Howard, Jonathan C. Schwemmle, Martin Steinfeldt, Tobias Nat Commun Article Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1(CIM) to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1(CIM), indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors. Nature Publishing Group UK 2019-03-15 /pmc/articles/PMC6420625/ /pubmed/30874554 http://dx.doi.org/10.1038/s41467-019-09200-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Murillo-León, Mateo
Müller, Urs B.
Zimmermann, Ines
Singh, Shishir
Widdershooven, Pia
Campos, Cláudia
Alvarez, Catalina
Könen-Waisman, Stephanie
Lukes, Nahleen
Ruzsics, Zsolt
Howard, Jonathan C.
Schwemmle, Martin
Steinfeldt, Tobias
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
title Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
title_full Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
title_fullStr Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
title_full_unstemmed Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
title_short Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
title_sort molecular mechanism for the control of virulent toxoplasma gondii infections in wild-derived mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420625/
https://www.ncbi.nlm.nih.gov/pubmed/30874554
http://dx.doi.org/10.1038/s41467-019-09200-2
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