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The brain and meningeal spaces are protected from bacterial invasion by the blood-brain barrier, formed by specialized endothelial cells and tight intercellular junctional complexes. However, once in the bloodstream, Neisseria meningitidis crosses this barrier in about 60% of the cases. This highlights the particular efficacy with which N. meningitidis targets the brain vascular cell wall. The first step of central nervous system invasion is the direct interaction between bacteria and endothelial cells. This step is mediated by the type IV pili, which induce a remodelling of the endothelial monolayer, leading to the opening of the intercellular space. In this review, strategies used by the bacteria to survive in the bloodstream, to colonize the brain vasculature and to cross the blood-brain barrier will be discussed., (© 2012 Blackwell Publishing Ltd.)

Purpura fulminans (PF) is a dreadful and frequent complication of Neisseria meningitidis invasive infection, and is associated with a high mortality rate. This syndrome begins with dermal microvessels thrombosis that rapidly lead to hemorrhagic skin necrosis. In this review, we discuss the prothrombotic events occurring during meningococcal infection. Moreover, recent data from an experimental mouse model have highlighted the critical role of the meningococcus adhesion to the endothelium in the development of PF lesions, thus opening new therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis is an extracellular pathogen, which, once in the bloodstream, has the ability to form microcolonies on the apical surface of endothelia. Pathogen interaction with microvessels is mediated by bacterial type IV pili and two receptors on endothelial cells: CD147 and the β2-adrenoceptor. CD147 facilitates the adhesion of diplococci to the endothelium, whereas the β2-adrenoceptor facilitates cell signaling, and crossing of the blood–brain barrier. In this review, we discuss how meningococcal interaction with endothelial cells is responsible for the specific clinical features of invasive meningococcal infection such as meningitis, and a peripheral thrombotic/vascular leakage syndrome possibly leading to purpura fulminans. [ABSTRACT FROM AUTHOR]

Chronic meningococcemia is a form of sepsis with frequent polymorphous skin lesions. Both in vivo and in vitro data suggest that, in these lesions, meningococci gain access from the capillary lumen to the peripheral extravascular compartment, in the absence of vascular dislocation, through a paraendothelial route. [ABSTRACT FROM AUTHOR]

Type IV pili mediate the initial interaction of many bacterial pathogens with their host cells. In Neisseria meningitidis, the causative agent of cerebrospinal meningitis, type IV pili-mediated adhesion to brain endothelial cells is required for bacteria to cross the blood-brain barrier. Here, type IV pili-mediated adhesion of N. meningitidis to human brain endothelial cells was found to recruit the Par3/Par6/PKCζ polarity complex that plays a pivotal role in the establishment of eukaryotic cell polarity and the formation of intercellular junctions. This recruitment leads to the formation of ectopic intercellular junctional domains at the site of bacteria-host cell interaction and a subsequent depletion of junctional proteins at the cell-cell interface with opening of the intercellular junctions of the brain-endothelial interface. [ABSTRACT FROM AUTHOR]