1. Microbiology and Infectious Disease
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Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation

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Cite this article as: eLife 2018;7:e39887 doi: 10.7554/eLife.39887

Abstract

The intracellular parasite Toxoplasma gondii, hijacks evolutionarily conserved host processes by delivering effector proteins into the host cell that shift gene expression in a timely fashion. We identified a parasite dense granule protein as GRA18 that once released in the host cell cytoplasm forms versatile complexes with regulatory elements of the β-catenin destruction complex. By interacting with GSK3/PP2A-B56, GRA18 drives β-catenin up-regulation and the downstream effects on host cell gene expression. In the context of macrophages infection, GRA18 induces the expression of a specific set of genes commonly associated with an anti-inflammatory response that includes those encoding chemokines CCL17 and CCL22. Overall, this study adds another original strategy by which T. gondii tachyzoites reshuffle the host cell interactome through a GSK3/β-catenin axis to selectively reprogram immune gene expression.

Article and author information

Author details

  1. Huan He

    Team Host-pathogen interactions and Immunity to Infection, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Marie-Pierre Brenier-pinchart

    Team Host-pathogen interactions and Immunity to Infection, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Laurence Braun

    Team Host-pathogen interactions and Immunity to Infection, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandra Kraut

    Institut de Biosciences et Biotechnologies de Grenoble, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Bastien Touquet

    Team Membrane and Cell Dynamics of Host Parasite Interactions, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Yohann Couté

    Institut de Biosciences et Biotechnologies de Grenoble, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3896-6196
  7. Isabelle Tardieux

    Team Membrane and Cell Dynamics of Host Parasite Interactions, Université Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Mohamed-ali Hakimi

    Team Host-pathogen interactions and Immunity to Infection, Université Grenoble Alpes, Grenoble, France
    For correspondence
    mohamed-ali.hakimi@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2547-8233
  9. Alexandre Bougdour

    Team Host-pathogen interactions and Immunity to Infection, Université Grenoble Alpes, Grenoble, France
    For correspondence
    alexandre.bougdour@univ-grenoble-alpes.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5895-0020

Funding

Agence Nationale de la Recherche (ANR-12-JSV3-0004-01)

  • Alexandre Bougdour

European Commission (ERC Consolidator Grant No. 614880)

  • Laurence Braun
  • Mohamed-ali Hakimi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed under pathogen-free conditions in accordance with established institutional guidance and approved protocols from the institutional animal care and use committee protocol (#175_UHTA-UMR5163-AB-01) of the University Grenoble Alpes. For all the experiments performed, every effort was made to minimize suffering.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: July 6, 2018
  2. Accepted: October 14, 2018
  3. Accepted Manuscript published: October 15, 2018 (version 1)
  4. Version of Record published: November 2, 2018 (version 2)

Copyright

© 2018, He et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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