Heikenwalder, M; Zeller, N; Seeger, H; Prinz, M; Klöhn, P C; Schwarz, Petra; Ruddle, N H; Weissmann, Charles; Aguzzi, A (2005). Chronic lymphocytic inflammation specifies the organ tropism of prions. Science, 307(5712):1107-1110.
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Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-alpha or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.
|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology
610 Medicine & health
|Date:||18 February 2005|
|Deposited On:||11 Feb 2008 12:25|
|Last Modified:||23 Nov 2012 15:53|
|Publisher:||American Association for the Advancement of Science (AAAS)|
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