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Nat Med. 2014 Jul;20(7):725-31. doi: 10.1038/nm.3563. Epub 2014 Jun 1.

Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization.

Author information

1
1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Université Paris Diderot, Paris, France. [5].
2
1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] [5].
3
1] INSERM, U1151, Institut Necker Enfants Malades, Paris, France. [2] CNRS, UMR8253, Paris, France. [3] Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France.
4
1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
5
1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
6
1] Unité Histopathologie Humaine et Modèles Animaux, Institut Pasteur, Paris, France. [2] Faculté de Médecine, Université Versailles Saint-Quentin-en-Yvelines, Versailles, France. [3] Assistance Publique-Hôpitaux de Paris, Hôpital Raymond Poincaré, Paris, France.
7
BMYscreen, INSERM U1053, Université de Bordeaux, Bordeaux, France.
8
1] Cellular Microbiology of Infectious Pathogens, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France. [2] CNRS UM8204, Lille, France. [3] INSERM U1019, Lille, France. [4] BioImaging Center Lille (BICeL), Université Lille Nord de France, Lille, France.
9
1] INSERM, U1151, Institut Necker Enfants Malades, Paris, France. [2] CNRS, UMR8253, Paris, France. [3] Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Abstract

Neisseria meningitidis is a cause of meningitis epidemics worldwide and of rapidly progressing fatal septic shock. A crucial step in the pathogenesis of invasive meningococcal infections is the adhesion of bloodborne meningococci to both peripheral and brain endothelia, leading to major vascular dysfunction. Initial adhesion of pathogenic strains to endothelial cells relies on meningococcal type IV pili, but the endothelial receptor for bacterial adhesion remains unknown. Here, we report that the immunoglobulin superfamily member CD147 (also called extracellular matrix metalloproteinase inducer (EMMPRIN) or Basigin) is a critical host receptor for the meningococcal pilus components PilE and PilV. Interfering with this interaction potently inhibited the primary attachment of meningococci to human endothelial cells in vitro and prevented colonization of vessels in human brain tissue explants ex vivo and in humanized mice in vivo. These findings establish the molecular events by which meningococci target human endothelia, and they open new perspectives for treatment and prevention of meningococcus-induced vascular dysfunctions.

PMID:
24880614
DOI:
10.1038/nm.3563
[Indexed for MEDLINE]

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