Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures.
Neisseria meningitidis elicits the formation of membrane protrusions on vascular endothelial cells, enabling its internalization and transcytosis. We provide evidence that this process interferes with the transendothelial migration of leukocytes. Bacteria adhering to endothelial cells actively recruit ezrin, moesin, and ezrin binding adhesion molecules. These molecules no longer accumulate at sites of leukocyte-endothelial contact, preventing the formation of the endothelial docking structures required for proper leukocyte diapedesis. Overexpression of exogenous ezrin or moesin is sufficient to rescue the formation of docking structures on and leukocyte migration through infected endothelial monolayers. Inversely, expression of the dominant-negative NH(2)-terminal domain of ezrin markedly inhibits the formation of docking structures and leukocyte diapedesis through noninfected monolayers. Ezrin and moesin thus appear as pivotal endothelial proteins required for leukocyte diapedesis that are titrated away by N. meningitidis. These results highlight a novel strategy developed by a bacterial pathogen to hamper the host inflammatory response by interfering with leukocyte-endothelial cell interaction.
Doulet
Nicolas
N
Département de Biologie Cellulaire, Institut Cochin, F-75014 Paris, France.
Donnadieu
Emmanuel
E
Laran-Chich
Marie-Pierre
MP
Niedergang
Florence
F
Nassif
Xavier
X
Couraud
Pierre Olivier
PO
Bourdoulous
Sandrine
S
D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D007962:Leukocytes / Q000378:metabolism* / Q000648:ultrastructure; D008585:Meningitis, Meningococcal / Q000503:physiopathology; D008840:Microfilament Proteins / Q000378:metabolism; D009345:Neisseria meningitidis / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D000099149:Ezrin
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin