NR AXOF
AU Heikenwälder,M.; Margalith,I.; Julius,C.; Polymenidou,M.; Haybäck,J.; Marcel,A.; Schwarz,P.; Kurrer,M.; Aguzzi,A.
TI Granulomas Induce Prion Replication Competence Independent of Follicular Dendritic Cells
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC3.5
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB Prions colonize organs of the central nervous and the immune system, both in animals and humans. It was recently demonstrated that chronic lymphofollicular inflammations alter the tropism of prions, thereby transforming organs previously believed to be devoid of prions (e.g. pancreas, kidney, liver, mammary gland) into sites of prion accumulation 1,2. Additionally, other conditions of inflammation or lymphoproliferative disorders (e.g. inclusion body myositis; lymphoma) were demonstrated to accumulate abundant PrPsc 3,4. Here we investigated whether granuloma, extremely common in ruminants and other species, induce ectopic prion accumulation and replication. Granuloma were induced subcutaneously in wild-type, PrPc overexpressing and Prnpo/o mice prior to intraperitoneal prion administration. Induced granuloma contained prominent immunohistochemical and molecular hallmarks similar to those found in humans. In contrast to spleens and granulomas of peripherally infected Prnpo/o mice, wild-type mice showed PrPsc and prion infectivity in spleens and granulomas investigated at various time points post prion inoculation (50 or 90dpi). Skin homogenates isolated form the identical animals were shown to be devoid of prion infectivity. Histoblot analysis identified the presence of PrPsc in granulomatous nodules of wild-type but not PrPo/o mice. Here, we describe replication of prion infectivity in the absence of mature FDCs and identify the compartment responsible for prion replication in granulomas. These data indicate that granulomas can be sites of prion infectivity and point to a novel mechanism of peripheral prion replication.
AD M. Heikenwälder, University Hospital Zürich, Pathology, Switzerland; I. Margalith, C. Julius, M. Polymenidou, J. Haybäck, A. Marcel, P. Schwarz, M. Kurrer, A. Aguzzi, Pathology, Inst. for Neuropathology, Switzerland
SP englisch
PO Schottland