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Originally published in Science Express on 20 January 2005
Science 18 February 2005:
Vol. 307. no. 5712, pp. 1107 - 1110
DOI: 10.1126/science.1106460
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Reports

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

Mathias Heikenwalder,1* Nicolas Zeller,1* Harald Seeger,1* Marco Prinz,1*{dagger} Peter-Christian Klöhn,2 Petra Schwarz,1 Nancy H. Ruddle,3 Charles Weissmann,2 Adriano Aguzzi1{ddagger}

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.

1 Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
2 Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
3 Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

* These authors contributed equally to this work.

{dagger} Present address: Institute of Neuropathology, Georg-August-Universität, D-37073 Göttingen, Germany.

{ddagger} To whom correspondence should be addressed. E-mail: adriano{at}pathol.unizh.ch

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