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Published Online January 20, 2005
Science DOI: 10.1126/science.1106460

Reports

Submitted on October 18, 2004
Accepted on December 6, 2004

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

Mathias Heikenwalder 1, Nicolas Zeller 1, Harald Seeger 1, Marco Prinz 2, Peter-Christian Klöhn 3, Petra Schwarz 1, Nancy H. Ruddle 4, Charles Weissmann 3, Adriano Aguzzi 2*

1 Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
2 Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland; Present address: Institute of Neuropathology, Georg-August-Universität, D-37073 Göttingen, Germany.
3 Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
4 Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

* To whom correspondence should be addressed.
Adriano Aguzzi , E-mail: adriano{at}pathol.unizh.ch

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 kidney, pancreas or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin upregulation and ectopic induction of PrPC-expressing FDC-M1+ cells, whereas inflamed organs of mice lacking lymphotoxin-{alpha} or its receptor did not accumulate PrPSc nor infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.


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