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Horst Schroten | Christian Schwerk

Innate immunity and the blood-brain barriers

The blood-brain barriers consist of endothelial and epithelial cells and protect the central nervous system from toxic substances, invading pahogens and metastasizing tumor cells, and regulate the entry of immune cells during health and disease. Amongst other things, host cells react to infection and disease conditions by regulation of gene expression and contribute to the immune response by producing cytokines and chemokines and the expression of surface receptors.

Using in vitro models of the blood-brain barriers we investigate the cellular response under pathogenic conditions. Our aims are to identify the mechanisms and signal transduction pathways involved in the control of gene expression and barrier function, and to shed light on the regulation of immune and cancer cell transmigration across the barriers.

Studies in an in vitro model of the blood-cerebrospinal fluid barrier. (A) Neisseria meningitidis (magenta) attached to the apical side of the blood-cerebrospinal fluid barrier. (B) A polymorphnuclear neutrophil (PMN) paracellularly transmigrating the epithelium (PE) of the blood-cerebrospinal fluid barrier. Arrows indicate hemidesmosomes. (C) A CellTracker-stained neuroblastoma cell (yellow) crossing the blood-cerebrospinal fluid barrier.

Publications

Vandenhaute, E., Stump-Guthier, C., Lasierra Losada, M., Tenenbaum, T., Rudolph, H., Ishikawa, H., Schwerk, C., Schroten, H., Dürken, M., März, M., and Karremann, M. (2015). The choroid plexus may be an underestimated site of tumor invasion to the brain: an in vitro study using neuroblastoma cell lines. Cancer Cell Int. 15, 102.

Schwerk, C., Tenenbaum, T., Kim, K.S., and Schroten, H. (2015). The choroid plexus-a multi-role player during infectious diseases of the CNS. Front. Cell. Neurosci. 9, 80.

Borkowski, J., Li, L., Steinmann, U., Quednau, N., Stump-Guthier, C., Weiss, C., Findeisen, P., Gretz, N., Ishikawa, H., Tenenbaum, T., Schroten, H., and Schwerk, C. (2014). Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model. J. Neuroinflammation 11, 163.

Steinmann, U., Borkowski, J., Wolburg, H., Schröppel, B., Findeisen, P., Weiss, C., Ishikawa, H., Schwerk, C., Schroten, H., and Tenenbaum, T. (2013). Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal-fluid barrier after bacterial infection in vitro. J. Neuroinflammation 10, 31.

Schwerk, C., Papandreou, T., Schuhmann, D., Nickol, L., Borkowski, J., Steinmann, U., Quednau, N., Stump, C., Weiss, C., Berger, J., Wolburg, H., Claus, H., Vogel, U., Ishikawa, H., Tenenbaum, T., and Schroten, H. (2012). Polar invasion and translocation of Neisseria meningitidis and Streptococcus suis in a novel human model of the blood-cerebrospinal fluid barrier. PLoS ONE 7, e30069.

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