Galectin-3, a marker for vacuole lysis by invasive pathogens

Authors

  • Irit Paz,

    1. Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris, Cedex 15, France.
    2. Unité INSERM 786, Institut Pasteur, 25-28 rue du Dr Roux, Paris, Cedex 15, France.
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  • Martin Sachse,

    1. Platform of Ultrastructural Microscopy, Institut Pasteur, 25-28 rue du Dr Roux, Paris, Cedex 15, France.
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  • Nicolas Dupont,

    1. Cellular Microbiology and Infectious Pathogeny UMR8161 (CNRS, Lille Pasteur Institute, Universities Lille 1 and Lille 2), Lille Biology Institute, Lille Pasteur Institute, Lille, France.
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  • Joelle Mounier,

    1. Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris, Cedex 15, France.
    2. Unité INSERM 786, Institut Pasteur, 25-28 rue du Dr Roux, Paris, Cedex 15, France.
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  • Cecilia Cederfur,

    1. Section MIG (Microbiology Immunology Glycobiology), Institute Laboratory Medicine, Lund University, Lund, Sweden.
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  • Jost Enninga,

    1. Institut Pasteur, Groupe ‘Dynamique des interactions hôte-pathogène’, 25 rue du Dr Roux, 75724, Paris, France.
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  • Hakon Leffler,

    1. Section MIG (Microbiology Immunology Glycobiology), Institute Laboratory Medicine, Lund University, Lund, Sweden.
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  • Francoise Poirier,

    1. Laboratoire de Genetique et Developpement des Mammiferes, Institut Jacques Monod, UMR CNRS 7592, Universités Paris 6 and Paris 7, Paris, France.
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  • Marie-Christine Prevost,

    1. Platform of Ultrastructural Microscopy, Institut Pasteur, 25-28 rue du Dr Roux, Paris, Cedex 15, France.
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  • Frank Lafont,

    1. Cellular Microbiology and Infectious Pathogeny UMR8161 (CNRS, Lille Pasteur Institute, Universities Lille 1 and Lille 2), Lille Biology Institute, Lille Pasteur Institute, Lille, France.
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  • Philippe Sansonetti

    Corresponding author
    1. Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris, Cedex 15, France.
    2. Unité INSERM 786, Institut Pasteur, 25-28 rue du Dr Roux, Paris, Cedex 15, France.
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*E-mail psanson@pasteur.fr; Tel. (+33) 1 45 68 83 42; Fax (+33) 1 45 68 89 53.

Summary

Shigella bacteria invade macrophages and epithelial cells and following internalization lyse the phagosome and escape to the cytoplasm. Galectin-3, an abundant protein in macrophages and epithelial cells, belongs to a family of beta-galactoside-binding proteins, the galectins, with many proposed functions in immune response, development, differentiation, cancer and infection. Galectins are synthesized as cytosolic proteins and following non-classical secretion bind extracellular beta-galactosides. Here we analysed the localization of galectin-3 following entry of Shigella into the cytosol and detected a striking phenomenon. Very shortly after bacterial invasion, intracellular galectin-3 accumulated in structures in vicinity to internalized bacteria. By using immuno-electron microscopy analysis we identified galectin-3 in membranes localized in the phagosome and in tubules and vesicles that derive from the endocytic pathway. We also demonstrated that the binding of galectin-3 to host N-acetyllactosamine-containing glycans, was required for forming the structures. Accumulation of the structures was a type three secretion system-dependent process. More specifically, existence of structures was strictly dependent upon lysis of the phagocytic vacuole and could be shown also by Gram-positive Listeria and Salmonella sifA mutant. We suggest that galectin-3-containing structures may serve as a potential novel tool to spot vacuole lysis.

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