NR AOUU
AU Klein,M.A.
TI The neuroimmune connection in prion diseases
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-26
PT Konferenz-Vortrag
AB The pathophysiological sequences which lead from the uptake of prions to the clinical disease in the nervous system are not understood in detail. Accumulating evidence indicates that the peripheral nervous system and the immune system are involved in the transfer of the infectious agent. Following peripheral routes of inoculation, infectivity accumulates very rapidly in the follicular dendritic network composed of follicular dendritic cells (FDC) and B-lymphocytes in the germinal centers of secondary lymphoid structures. Immunodeficient mice which lack mature B-cells are resistant to scrapie after intraperitoneal inoculation and mature B cells are required for prion propagation in lymphoid tissue, not because they themselves harbour or multiply prions, but they are required for maintenance of the FDC network. The accumulation of prions within the FDC network is similar to the acquisition and retention of antigens in lymphoid organs. Therefore we investigated the role of the complement system, a part of the innate arm of the immune system, in peripheral prion pathogenesis. We found that early components of the complement system facilitate prion transport to the nervous system. The expression of PrPc on FDC in the spleen is a prerequisite for prion propagation but the physiological role of PrPc in periphery is elusive. Recently, we performed a detailed analysis on the role and function of PrPc expression in the lymphoid system. Independent of the PrPc expression levels in the germinal centers, we detected a constitutive expression of PrPc in the splenic capsule and trabeculae. Furthermore an up-regulation of PrPc-expression in the FDC network after stimulation with preformed immune complexes or viral infection was evident depending on the presence of complement factor C1q. These findings may be critical steps in the search of physiological functions of PrP, as well as in the determination for its role in peripheral prion pathogenesis.
AD Michael A. Klein, University of Würzburg
SP englisch
PO Deutschland