title: Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization.
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.
authors.affiliation: 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].
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Bernard
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] [5].
authors.forename: Nandi
authors.initials: N
authors.lastname: Simpson
authors.affiliation: 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.
authors.forename: Olivier
authors.initials: O
authors.lastname: Join-Lambert
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Federici
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Laran-Chich
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Nawal
authors.initials: N
authors.lastname: Maïssa
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Haniaa
authors.initials: H
authors.lastname: Bouzinba-Ségard
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Philippe C
authors.initials: PC
authors.lastname: Morand
authors.affiliation: 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.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chretien
authors.affiliation: BMYscreen, INSERM U1053, Université de Bordeaux, Bordeaux, France.
authors.forename: Saïd
authors.initials: S
authors.lastname: Taouji
authors.affiliation: BMYscreen, INSERM U1053, Université de Bordeaux, Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.affiliation: 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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Janel
authors.affiliation: 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.
authors.forename: Frank
authors.initials: F
authors.lastname: Lafont
authors.affiliation: 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.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coureuil
authors.affiliation: 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.
authors.forename: Audrey
authors.initials: A
authors.lastname: Segura
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Niedergang
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marullo
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: Nassif
authors.affiliation: 1] INSERM, U1016, Institut Cochin, Paris, France. [2] CNRS, UMR8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bourdoulous
mesh_terms: D001422:Bacterial Adhesion; D051926:Basigin / Q000276:immunology*; D001808:Blood Vessels / Q000382:microbiology*; D010861:Fimbriae, Bacterial / Q000502:physiology; D006801:Humans; D009345:Neisseria meningitidis / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D051926:Basigin