NR ARDR
AU Sethi,S.K.; Kerksieck,K.M.; Nopora,A.; Hinske,H.; Brocker,T.; Kretzschmar,H.A.
TI Role of B cells and dendritic cells after oral and intraperitoneal transmission of scrapie
QU TSE-Forum, 4. Kongress - Nationale TSE-Forschungsplattform, Düsseldorf 28.10.-29.10.2004, Poster PATH-05
PT Konferenz-Poster
AB Lymphoid tissues are deeply involved in the pathogenesis of prion diseases. However, controversial results have been observed in different mouse models regarding the role of lymphoid tissues in prion pathogenesis. Using the intraperitoneal route, a crucial role for B lymphocytes and follicular dendritic cells (FDC) has been established in prion pathogenesis. However the experimental data regarding the role of these cells is not conclusive. The link between FDC and prion spread to the CNS also remains unclear. How prions reach peripheral nerve endings from FDC located in the germinal center is unclear, as mature FDC do not move from the germinal center. It had been shown previously that CD11c+ dendritic cells (DC) can propagate prions from the periphery to the CNS, making CD11c+ DC a likely carrier for prions. In order to study oral and intraperitoneal scrapie pathogenesis we used a novel mouse model to investigate the role of DC and B cells. Transgenic CD19-N17Rac1 mice express a dominant negative variant of Rac-1 under the control of a B cell specific CD19 promoter. When transgenic mice CD19-N17Rac1 (low copy) mice were infected intraperitoneally, they developed disease as well as CD19-N17Rac1 mice (high copy), which were infected orally. Transgenic mice (CD11c-N17Rac1) expressing dominant negative variants of Rac-1 in DC showed a dramatic reduction in CD8+ CD11chi DC and a defect in endocytosis. Transgenic mice (CD11c-N17Rac1) developed scrapie after intraperitoneal and oral inoculation with the RML prion strain. Using the intraperitoneal route of infection CD11c-N17Rac1 mice had somewhat longer incubation times than the respective controls. These results indicate that CD8+ CD11chi DC are not absolutely required for scrapie pathogenesis in intraperitoneal and oral infection with the RML strain in this mouse model and that their are possibly differences in the role of DC in oral versus intraperitoneal scrapie pathogenesis. Further experiments are currently in progress to investigate the role of DC using the ME7 prion strain.
AD Shneh Sethi, Christian Hinske, Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität, München, Germany; Kerstin Kerksieck, Adam Nopora, Thomas Brocker, Hans A. Kretzschmar, Institut für Immunologie, Ludwig-Maximilians-Universität, München, Germany
SP englisch
PO Deutschland
OR Tagungsband