Published 22 May 2006. doi:10.1083/jcb.200507128
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 173, Number 4, 627-637
Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures
Nicolas Doulet1,2,3,4,
Emmanuel Donnadieu1,2,3,4,
Marie-Pierre Laran-Chich1,2,3,4,
Florence Niedergang1,2,3,4,
Xavier Nassif5,
Pierre Olivier Couraud1,2,3,4, and
Sandrine Bourdoulous1,2,3,4
1 Département de Biologie Cellulaire, Institut Cochin, F-75014 Paris, France
2 Institut National de la Santé et de la Recherche Médicale, U567, F-75014 Paris, France
3 Centre National de la Recherche Scientifique, UMR 8104, F-75014 Paris, France
4 Université Paris Descartes, Faculté de Médecine René Descartes, UMR-S 8104, F-75014 Paris, France
5 Laboratoire de Microbiologie, Institut National de la Santé et de la Recherche Médicale U570, 75015 Paris, France
Correspondence to Sandrine Bourdoulous: bourdoulous{at}cochin.inserm.fr
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 NH2-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.
Abbreviations used in this paper: ERM, ezrin-radixin-moesin; HBMEC, human bone marrow endothelial cell line; ICAM, intracellular adhesion molecule; SDF, stromal cell–derived factor; VCAM, vascular cell adhesion molecule.
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