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

Billel Benmimoun, Florentia Papastefanaki, Bruno Périchon, Katerina Segklia, Nicolas Roby, Vivi Miriagou, Christine Schmitt, Shaynoor Dramsi, Rebecca Matsas and Pauline Spéder ()
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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

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19826-2

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