Mechanism Of Meningeal Invasion By Neisseria Meningitidis

SPECIAL FOCUS REVIEW: BLOOD-BRAIN BARRIER
Virulence 3:2, 1–9; March/April 2012;
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2012 Landes Bioscience

Mechanism of meningeal invasion by Neisseria meningitidis
Mathieu Coureuil,1,2 Olivier Join-Lambert,1,2,3 Hervé Lécuyer,1,2,3 Sandrine Bourdoulous,2,4,5 Stefano Marullo2,4,5 and Xavier Nassif1,2,3,*
1

INSERM U1002; Paris, France; 2Université Paris Descartes; Sorbonne Paris Cité;Faculté de Médecine; Paris, France; 3Assistance Publique; Hôpitaux de Paris; Hôpital Necker Enfants Malades; Paris, France; 4INSERM U1016; Institut Cochin; Paris, France; 5CNRS UMR8104; Paris, France

© 2012 Landes Bioscience. Do not distribute.
Introduction Bacterial meningitis is the leading cause of central nervous system (CNS) infection. Although bacterial meningitis can be due to thedissemination of contiguous infections such as sinusitis or mastoiditis to the meningeal membranes, most cases are caused by blood-borne pathogens. The blood-brain barrier (BBB) protects the CNS from most bacteria that may have reached the bloodstream, thus restricting the etiology of bacterial meningitis to a few and predominantly extracellular pathogens: Escherichia coli K1 and Streptococcusagalactiae (Group B Streptococcus) in the newborn, Neisseria meningitidis, Haemophilus influenzae type b and Streptococcus pneumoniae in children and adults.1-3 Paradoxically, these bacteria are commensal of the nasopharynx (N. meningitidis, S. pneumoniae and H. influenzae) or of the digestive tract (E. coli and S. agalactiae).4 The pathophysiology of bacterial meningitis is a multistep process thatreflects the ability of bacterial pathogens to cross the oropharyngeal or digestive mucosal barrier, survive and replicate in the bloodstream, and to eventually cross the BBB.4-6 It has been demonstrated that these extracellular pathogens express various
*Correspondence to: Xavier Nassif; Email: xavier.nassif@inserm.fr Submitted: 09/14/11; Revised: 11/02/11; Accepted: 11/03/11http://dx.doi.org/10.4161/viru.3.2.18639

The blood-cerebrospinal fluid barrier physiologically protects the meningeal spaces from blood-borne bacterial pathogens, due to the existence of specialized junctional interendothelial complexes. Few bacterial pathogens are able to reach the subarachnoidal space and among those, Neisseria meningitidis is the one that achieves this task the most constantly when present in thebloodstream. Meningeal invasion is a consequence of a tight interaction of meningococci with brain endothelial cells. This interaction, mediated by the type IV pili, is responsible for the formation of microcolonies on the apical surface of the cells. This interaction is followed by the activation of signaling pathways in the host cells leading to the formation of endothelial docking structuresresembling those elicited by the interaction of leukocytes with endothelial cells during extravasation. The consequence of these bacterialinduced signaling events is the recruitment of intercellular junction components in the docking structure and the subsequent opening of the intercellular junctions.

virulence factors allowing them to survive in the extracellular compartments and to interactdirectly with the components of the blood-brain barrier. The main virulence factor expressed by all extracellular pathogens is a capsule that prevents bacterial phagocytosis or complement-mediated lysis.4,7-12 Once inside the CSF, bacterial multiplication is thought to be uncontrolled, due to the local deficiency in complement and immunoglobulins, despite the influx of polymorphonuclear leukocytesinduced by the local inflammatory response. However data obtained in primates showed that bacterial presence in the CSF can be transient if bacteremia is not sustained, reflecting the fact that bacterial entry into the CSF may not always lead to meningitis.13 The small number of bacterial species capable of invading the meninges suggests that specific virulence factors are required for bacteria to...