Integrin-mediated signal transduction in brain endothelial cells during infection with N. meningitidis: mechanisms of crossing the blood-brain barrier

• Applicant: Professorin Dr. Alexandra Schubert-Unkmeir
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2007 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 50684542

Neisseria meningitidis colonizes the nasopharynx, from which it can seed the bloodstream before crossing the blood-brain barrier to cause meningitis. We showed that N. meningitidis induces the release of the matrix metalloproteinase (MMP)-8, that plays a crucial role in disassembly of the tight junction (TJ) component occludin and loss of cell adhesion. The proposed project aims to investigate the expression and regulation of MMP-8 in brain endothelial cells in response to N. meningitidis infection. The specific effect of bacterial factors on loss of cell adhesion and occludin cleavage will be analysed as well as the regulation/protection of cell monolayers by different treatments (dexamethason, chemically modified tetracyclines). Furthermore, activation of the epidermal growth factor receptor (EGFR), a transmembrane receptor kinase, during the early step of adhesion was observed. The second part of the projects aims to analyse the role of EGFR in adhesion/invasion process of N. meningitidis. Bacterial factors that bind to EGFR shall be identified as well as EGFR-mediated cell signalling events with specific focus on the EGFR/integrin crosstalk.

• DFG Programme: Research Grants