Mechanisms of meningeal invasion by a bacterial extracellular pathogen, the example of Neisseria meningitidis.
The blood-cerebrospinal fluid (CSF) barrier physiologically protects the meningeal spaces from bloodborne bacterial pathogens, due to the existence of specialized junctional interendothelial complexes. A few bacterial pathogens are able to reach the subarachnoidal space and cause bacterial meningitis in humans, a rare but dreadful disease. Surprisingly, most of them are extracellular commensals of the nasopharynx (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) or of the digestive tract (Escherichia coli and Streptococcus agalactiae). The particular ability of these pathogens to induce meningitis is related to virulence factors that allow them to escape host innate immunity, to multiply within the serum, and to interact closely with the endothelial front line of defense of the blood-CSF barrier. In vitro studies using microvascular brain endothelial cell lines have shown that induced transcytosis may be a common route used by H. influenzae, S. pneumoniae, E. coli and S. agalactiae to reach the CSF. N. meningitidis is a strict human pathogen that interacts very tightly with endothelial cells. Adhesion of the meningococcus is mediated by type IV pili that induce a localized remodeling of the sub cortical cytoskeleton, leading to the formation of endothelial membrane protrusions that anchor bacterial colonies at the endoluminal face of the endothelial cell membrane, allowing a better resistance to blood flow. Recent work has shown that N. meningitidis is also able to recruit the polarity complex Par3/Par6/aPKC that re-routes endothelial cell adhesion molecules of interendothelial junctions, opening a paracellular route for bacteria to cross the endothelial barrier.
Join-Lambert
Olivier
O
INSERM, Unité 570, 156 rue de Vaugirard, 75015 Paris, France. olivier.join-lambert@inserm.fr
Morand
Philippe C
PC
Carbonnelle
Etienne
E
Coureuil
Mathieu
M
Bille
Emmanuelle
E
Bourdoulous
Sandrine
S
Nassif
Xavier
X
D000818:Animals; D001812:Blood-Brain Barrier / Q000382:microbiology* / Q000503:physiopathology*; D006801:Humans; D008578:Meninges / Q000382:microbiology* / Q000503:physiopathology*; D008954:Models, Biological; D009345:Neisseria meningitidis / Q000502:physiology*