Die Interaktion von pathogenen Neisserien mit Endothelzellen und ihre Rolle bei der Überwindung der Blut-Hirn-Schranke

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Neisseria meningitidis, a gram-negative microorganism specialised to live within the human population, bears the potential for a deadly disease, bacterial meningitis. This pathogen is characterised by its ability to circumvent host bactericidal mechanisms and to cross the blood-brain barrier to infect the central nervous system. As a pre-requisite, meningococci have to interact with the endothelial lining of the brain vasculature to gain access to the meninges. Though several key components enabling these bacteria to escape the immune defence of healthy humans have been identified, it is still unclear which factors enable meningococci to establish tight contact with and to translocate through a layer of endothelial cells. With this project we would like to contribute to the understanding of N. meningitidis - endothelial cell interactions on the molecular level. In particular, we would like to investigate the meningococcal virulence factors contributing to attachment and invasion into endothelial cells and to the transcytosis through an endothelial layer. As the pathogenetic process of bacterial meningitis also depends on the contribution of host components, we will study the response of infected endothelial cells with regard to intracellular signal transduction events, gene expression, and ability to interact with circulating cells of the immune system. This combined approach will allow us to reconstruct the sequence of events occurring at the pathogen - endothelium interface and will enable us to point out key determinants of this process that could be sensitive to intervention.