Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization

Abstract

Neisseria meningitidis is the causative agent of potentially fatal meningitis and septic shock, induced by bacterial colonization of blood vessels in the brain and the periphery. The endothelial cell receptor mediating meningococcal adhesion to blood vessels has previously been unknown. Here Sandrine Bourdoulous and colleagues report that CD147 expressed on human endothelial cells is a crucial mediator of N. meningitidis vascular colonization, providing new insight into some of the mechanisms that give rise to meningococcal disease.

Supplementary information

The online version of this article (doi:10.1038/nm.3563) contains supplementary material, which is available to authorized users.

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.

Supplementary information

The online version of this article (doi:10.1038/nm.3563) contains supplementary material, which is available to authorized users.