Interaction of Neisseria meningitidis with cells of the human blood brain barrier

• Applicant: Professorin Dr. Alexandra Schubert-Unkmeir
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2002 to 2005
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5390048

The interaction of N. meningitidis with cells of the blood-brain barrier plays a pivotal role for invasion of the cerebrospinal fluid (CSF) and is thought to be the prerequisite for the strong inflammation of the leptomeninges. Our previous work using endothelial cells from human brain capillaries (HBMEC) as an in vitro culture model demonstrated that a trifactorial interaction is essential for uptake of meningococci by HBEMC and passage through the blood-brain barrier: the internalisation depends on the expression of the adhesin Opc and includes fibronectin as a human serum derived internalisation promoting factor which anchors the meningococcus to a specific intergrin receptor (a5b1 integrin) on the cell (E1). The molecular effects of these complex interactions are still unknown. The characterization of the ligand-receptor interaction and the subsequent induction of intracellular signalling cascades and gene expression in the cerebral endothelial cell will be the major objective of our future work. The manipulation of host signalling pathways by Neisseria meningitidis may reveal the basis of host colonisation and elucidate the events in the endothelial cell of the blood brain barrier that lead to serious disease conditions. These investigations will further contribute to the molecular understanding of the invasion of the blood brain barrier by meningococci and form the basis for the development of new therapeutic target molecules for prophylaxis and therapy of meningococcal menigitis.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1130: Infections of the Endothelium
• Participating Person: Professor Dr. Martin Eigenthaler