Molecular Characterization of Follicular Dendritic Cells, a Key Player in Prion Pathogenesis

Completed Research Project

Title / Titel: Molecular Characterization of Follicular Dendritic Cells, a Key Player in Prion Pathogenesis

Summary / Zusammenfassung: In the pathogenesis of scrapie and other transmissible spongiform encephalopathies (TSE) the immune system plays a central role. Following prion infection, both by intracerebral and intraperitoneal inoculation and also peripheral routes such as ingestion or through the skin, infectivity usually accumulates to high levels in the lymphoid tissues before becoming detectable in the central nervous system. Thus characterization of the cells supporting replication in these tissues is essential to understanding early pathogenesis and may indicate potential targets for therapy. Several previous studies indicate that the follicular dendritic cells (FDC) of the germinal centres of the spleen, lymph nodes and Peyer’s patches may play a key role in this process. In view of the central role of FDCs in prion pathogenesis the goal of this Project is to characterize FDCs on a molecular level and to find genes which are important for their function and biology and might be specifically expressed by them. To find such genes, mRNA expression levels in specimens containing or lacking FDCs are compared by either suppression subtractive hybridisation or microarray analysis. Identification of FDC-related genes will allow the isolation of transcriptional control regions (promoters and enhancers), which can be used as genetic tools to analyze the exact role of FDCs in a variety of diseases including TSE.

Keywords / Suchbegriffe: Follicular Dendritic Cells, Lymphoid Prion Accumulation, DNA Microarray Analysis

Project Leadership and Contacts / Projektleitung und Kontakte

Christoph Huber (Project Leader)	christoph.huber@usz.ch
Prof. A. Aguzzi	adriano@pathol.uzh.ch

Other Links to external Webpages: http://www.uzh.ch/pathol/neuropathologie/d/index.html

Funding Source(s) / Unterstützt durch: Other Public Sources (e.g. Federal or Cantonal Agencies), Foundation, Others
FAN, SBF, NCCR, Functional Genomics Center University Zürich

In Collaboration with / In Zusammenarbeit mit

Prof. E. Heinen, Immunology, University Liège

Belgium