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

Billel Benmimoun (1) , Florentia Papastefanaki (2) , Bruno Périchon (3) , Katerina Segklia (2) , Nicolas Roby (1) , Vivi Miriagou (2) , Christine Schmitt (4) , Shaynoor Dramsi (3) , Rebecca Matsas (2) , Pauline Spéder (1)

1 Plasticité cérébrale en Réponse à l'Environnement / Brain Plasticity In Response To The Environment
2 Institut Pasteur Hellénique
3 Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens
4 UTechS UBI - Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform

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.

Domaines: Microbiologie et Parasitologie

Billel Benmimoun, Florentia Papastefanaki, Bruno Périchon, Katerina Segklia, Nicolas Roby, et al.. An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing. Nature Communications, 2020, 11 (1), pp.6106. ⟨10.1038/s41467-020-19826-2⟩. ⟨pasteur-03037742⟩