NR AWGP
AU Heikenwalder,M.; Margalith,I.; Zeller,N.; Haybaeck,J.; Kurrer,M.; Aguzzi,A.
TI Granulomatous inflammation induces prion accumulation and replication
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-22
PT Konferenz-Poster
AB Prions colonize organs of the central nervous and the immune system, both in animals succumbing to prion diseases (e.g. scrapie; chronic wasting disease) and humans suffering from sporadic and variant Creutzfeldt-Jakob disease (sCJD; vCJD). Additionally, PrPsc and prion infectivity is present in muscle of sCJD patients and of elk and deer suffering from chronic wasting disease. We recently showed 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. However, lymphofollicular inflammation represents just one specific type of inflammatory morphology. Here, we investigated whether granulomatous inflammation, which is extremely common in ruminants and many other species, induces ectopic prion accumulation and replication. Granulomatous inflammation was induced subcutaneously in wild-type, PrPc overexpressing (tga20) and Prnpo/o mice prior to intraperitoneal administration of prions. Granulomatous nodules contained prominent immunohistochemical as well as molecular hallmarks of granulomatous inflammation similar to those found in humans, such as epitheloid macrophages, giant cells and upregulation of tumor necrosis factor. Surprisingly, levels of PrPc expression in granulomas rose to levels comparable to levels found in spleen. In contrast to spleens and granulomas of peripherally infected prnp-/- mice that were devoid of prion infectivity, wild-type as well as tga20 mice showed PrPsc and prion infectivity in all spleens and in up to 2/3 of all granulomas investigated. We found that prion accumulation and replication occurred despite the absence of morphologically and immunohistochemically recognizable FDCs. These data indicate that granulomatous inflammation can be an important site of prion replication and accumulation.
AD M. Heikenwalder, I. Margalith, N. Zeller, H. Haybaeck, A. Aguzzi: Institute of Neuropathology, Department of Pathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland; M. Kurrer: University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland
SP englisch
PO Italien