NR AOYC
AU Remer,K.A.; Flechsig,E.; Klein,M.A.
TI Up-take of prions by dendritic cells after exposure to mouse prions
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-23
PT Konferenz-Poster
AB
After oral uptake, prions enter the intestinal mucosa and infiltrate the adjacent lymphatic structures and enteric nerve fibers, where PrPsc is detectable early on. Dendritic cells (DC) are discussed as candidates for the transport of prions from the mucosa and are specialized in the initial up-take of antigens in the periphery.
The aim of this study is to investigate the role and the function of DC in the transport of RML mouse prions and the use of DC as an immunotherapeutic approach to prevent prion diseases. We have isolated bone marrow-derived immature DC from wild-type and Prnpo/o mice and exposed them to prion-infected brain homogenates in vitro. Cell blot assays show that bone marrow-derived immature DC of both genotypes take up PrPsc from brain homogenates most likely by a phagocytic mechanism. To examine, whether PrP-loaded DC are able to induce scrapie or an immune response against PrP in wild-type mice, immature DC of each genotype were pulsed with RML-infected brain homogenate, mock homogenate or recombinant PrP, and subcutaneously inoculated into C57BL/6 and Prnpo/o mice, respectively. Mice are currently monitored for the presence of PrPsc in lymphoid organs, onset of clinical symptoms and production of antibodies against PrP at various time points during the incubation period. Since spleens of RML-infected mice contain abundant PrPsc, we have further isolated mature DC from the spleens of RML-infected mice. Splenic DC are purified and analyzed for the presence of PrPsc by cell blot assay and Western blot and transferred into susceptible recipients to clarify their role in vivo.
AD K.A. Remer, E. Flechsig, M.A. Klein, Prion Research Group, Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany
SP englisch
PO Deutschland