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Physiopathology

Meningococcal Obstruction

Meningococcus is a common bacteria carried, without symptoms, by 10 to 15% of the population. However, this bacterium can provoke meningitis, an inflammation of the membrane covering the brain and spinal cord, a rare phenomenon in developed countries, but one that can reach epidemic proportions in Africa, affecting thousands of people with a case fatality rate of 10%. Drs. Sandrine Bourdoulous1 and Xavier Nassif's2 teams have recently revealed their findings on how virulent meningococci penetrate the endothelial cell barrier that lines local blood vessels (also called the Blood-Brain barrier), passing from the bloodstream to the brain.3

“The bacteria follow exactly the same path as the leukocytes (white blood cells), quite an advantage for them, since they are using a mechanism that is already established” says Bourdoulous. “The bacteria are thus able to penetrate the vascular wall through a process called transcytosis, while leukocytes cannot cross because their transfer mechanism has been blocked by the bacteria.” These bacteria thus delay the ability of leukocytes to cross the vascular wall from the blood to the cerebrospinal fluid, thus impeding an anti-infectious inflammatory response by the host.

These results have helped explain the process of leukocyte transendothelial migration that is central to this meningeal infection, and will no doubt open new avenues for prevention and treatment of the disease.

Future research will focus on detailing more specifically how the bacteria manage to cross the endothelial cell barrier. “The most exciting question involves finding the key receptor that participates in the initial interaction between the bacteria and the cell,” explains Bourdoulous. Identifying this receptor would be an important step toward designing new preventive vaccines.

 

Melisande Middleton

 

Notes :

1. Institut Cochin (CNRS/ Inserm / Université Paris-V joint lab).
2. Faculté de Médecine Necker–Enfants malades (Inserm / Université Paris-V joint lab).
3. Doulet et al., “Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures,” J. Cell Biol. 173: 627-637. 2006.

Contacts :

> Sandrine Bourdoulous
Institut Cochin, Paris.
bourdoulous@cochin.inserm.fr
> Xavier Nassif
Hôpital Necker–Enfants Malades, Paris.
nassif@necker.fr


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