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

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  • معلومة اضافية
    • Contributors:
      Plasticité cérébrale en Réponse à l'Environnement / Brain Plasticity In Response To The Environment; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Institut Pasteur Hellénique; Réseau International des Instituts Pasteur (RIIP); Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens; Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI); Institut Pasteur Paris (IP); This work has been funded by a starting package from Institut Pasteur/ LabEx Revive and a JCJC grant from Agence Nationale de la Recherche (NeuraSteNic, ANR- 17-CE13-0010-01) to P.S.; a Grand Projet Fédérateur Microbes & Brains InFeSteR grant from Institut Pasteur to P.S., R.M. and S.D. B.B. has been supported by a Roux-Cantarini (Institut Pasteur) and a LabEx Revive post-doctoral fellowships.; ANR-17-CE13-0018,NeuraSteNic,Interactions entre les cellules souches neurales et leur niche lors de la neurogenèse chez la drosophile(2017); ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010)
    • بيانات النشر:
      HAL CCSD
      Nature Publishing Group
    • الموضوع:
      2020
    • Collection:
      Institut Pasteur: HAL
    • نبذة مختصرة :
      International audience ; 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.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/33257684; pasteur-03037742; https://pasteur.hal.science/pasteur-03037742; https://pasteur.hal.science/pasteur-03037742/document; https://pasteur.hal.science/pasteur-03037742/file/s41467-020-19826-2.pdf; PUBMED: 33257684; PUBMEDCENTRAL: PMC7704634
    • الرقم المعرف:
      10.1038/s41467-020-19826-2
    • الدخول الالكتروني :
      https://pasteur.hal.science/pasteur-03037742
      https://pasteur.hal.science/pasteur-03037742/document
      https://pasteur.hal.science/pasteur-03037742/file/s41467-020-19826-2.pdf
      https://doi.org/10.1038/s41467-020-19826-2
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.2B8BA021