NR AOZC
AU Sethi,S.K.; Kerksieck,K.; Nopora,A.; Brocker,T.; Kretzschmar,H.A.
TI Enteric and intraperitoneal prion pathogenesis in mice with migratory deficiencies in B cells, FDCs and Dendritic cell populations
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-14
PT Konferenz-Poster
AB How prions enter the GI tract and the subsequent spread of prions to the CNS is not well understood. Using the intraperitoneal route a crucial role for B lymphocytes (Klein MA 1997) and FDCs (Mabbott 2000) has been established in scrapie pathogenesis. However, experimental data regarding the role of these cells is still not conclusive and other studies have indicated that neither cell type plays a crucial part in scrapie pathogenesis( Shlomchik 2001). Another cell type implicated in the pathogenesis of scrapie is the CD11c+ dendritic cell. The great part of the experimental data created till now has been obtained using the intraperitoneal route of infection, however such results cannot be simply transferred to the oral route (Prinz M 2003). Aim of this study was to investigate the role of B cells, FDCs and dendritic cells using a novel mouse model in which mice are infected that are transgenic for dominant negative variants of small GTPases. These inhibitory transgenes are expressed in either DCs (CD11c-promoter) or B cells/follicular DC (CD19-promoter). We infected CD19-N17rac1 low copy mice ( with a B cell restricted migration defect) and CD11c-N17Rac1 mice (with a defect in dendritic cells), intraperitoneally and orally. While i.p. infection always resulted in longer survival of transgenic mice as compared to controls, oral infection did not reveal strong differences. It further turned out that inhibition of B cells (CD19 construct) as well as inhibition of DC (CD11c-construct) revealed similar effects concerning time course of the disease. From these preliminary results it seems to be that the role of B cells and dendritic cells differs between i.p. and oral infection. One might also interpret these data in a way that not only one cell type (DC or B cells) seems to be responsible alone, but that both participate in one way or another in the spreading of the disease. For both routes detailed protein and histological studies are underway to investigate the spread of prions.
AD S.K. Sethi, H.A. Kretzschmar, Institute of Neuropathology, LMU,Munich, Germany; K. Kerksieck, A. Nopora, T. Brocker, Institute of Immunology,LMU, Munich, Germany
SP englisch
PO Deutschland