title: Meningococcal interaction to microvasculature triggers the tissular lesions of purpura fulminans.
abstract: Neisseria meningitidis is a strict human pathogen that closely interacts with human endothelial cells via type IV pili in vitro. To decipher whether this interaction plays a role in vivo, we set up an experimental model of fulminant meningococcemia in human skin grafted SCID mice using the wild-type strain 2C4.3. Human skin and mouse tissues were sampled 24 hours after bacterial challenge for histopathology, immunohistochemistry and ultrastructural analysis. In all infected mice, N. meningitidis targeted the human vasculature, leading to bacterial and blood thrombi, infectious vasculitis and vascular leakage. Mouse vessels, including brain vessels, remained unaffected by the infectious and thrombotic process, and a nonpiliated Δ pilE derivative of 2C4.3 failed to target human graft vessels and to induce vascular damages. These data demonstrate that N. meningitidis targets human endothelial cells in vivo and that this interaction triggers the vascular damages that characterize purpura fulminans.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1002, Paris.
authors.forename: Olivier
authors.initials: O
authors.lastname: Join-Lambert
authors.forename: Hervé
authors.initials: H
authors.lastname: Lecuyer
authors.forename: Florence
authors.initials: F
authors.lastname: Miller
authors.forename: Lucie
authors.initials: L
authors.lastname: Lelievre
authors.forename: Anne
authors.initials: A
authors.lastname: Jamet
authors.forename: Laetitia
authors.initials: L
authors.lastname: Furio
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.forename: Philippe
authors.initials: P
authors.lastname: Pelissier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coureuil
authors.forename: Xavier
authors.initials: X
authors.lastname: Nassif
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D042783:Endothelial Cells / Q000382:microbiology / Q000473:pathology; D004730:Endothelium, Vascular / Q000382:microbiology / Q000473:pathology; D005260:Female; D010861:Fimbriae, Bacterial / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008589:Meningococcal Infections / Q000150:complications / Q000382:microbiology; D051379:Mice; D055806:Microvessels / Q000382:microbiology* / Q000473:pathology; D009345:Neisseria meningitidis / Q000502:physiology*; D055665:Purpura Fulminans / Q000209:etiology* / Q000473:pathology*; D012867:Skin / Q000098:blood supply / Q000473:pathology; D016038:Skin Transplantation
keywords: Neisseria meningitidis; SCID mice; endothelial cells; infectious diseases; purpura fulminans; vascular infection; xenograft model