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An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing

Author

Listed:
  • Billel Benmimoun

    (Institut Pasteur, Brain Plasticity in Response to the Environment, CNRS)

  • Florentia Papastefanaki

    (Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Department of Neurobiology, Hellenic Pasteur Institute)

  • Bruno Périchon

    (Unité de Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur, CNRS)

  • Katerina Segklia

    (Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Department of Neurobiology, Hellenic Pasteur Institute)

  • Nicolas Roby

    (Institut Pasteur, Brain Plasticity in Response to the Environment, CNRS)

  • Vivi Miriagou

    (Laboratory of Bacteriology, Department of Microbiology, Hellenic Pasteur Institute)

  • Christine Schmitt

    (Ultrastructure UTechS Ultrastructural Bioimaging Platform, Institut Pasteur)

  • Shaynoor Dramsi

    (Unité de Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur, CNRS)

  • Rebecca Matsas

    (Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Department of Neurobiology, Hellenic Pasteur Institute)

  • Pauline Spéder

    (Institut Pasteur, Brain Plasticity in Response to the Environment, CNRS)

Abstract

Pathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We find that several mammalian pathogens are able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucine-rich Blr, are important for BBB crossing and virulence in Drosophila. Further, we identify (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we show that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results demonstrate the potential of Drosophila for studying BBB crossing by pathogens and identify a new mechanism by which pathogens exploit the machinery of host barriers to generate brain infection.

Suggested Citation

  • Billel Benmimoun & Florentia Papastefanaki & Bruno Périchon & Katerina Segklia & Nicolas Roby & Vivi Miriagou & Christine Schmitt & Shaynoor Dramsi & Rebecca Matsas & Pauline Spéder, 2020. "An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19826-2
    DOI: 10.1038/s41467-020-19826-2
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    Cited by:

    1. Maria Alexandra Rujano & David Briand & Bojana Ðelić & Julie Marc & Pauline Spéder, 2022. "An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-25, December.

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