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Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions
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 kidn...
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Published in: | Science (American Association for the Advancement of Science) 2005-02, Vol.307 (5712), p.1107-1110 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 PrP[superscript C]. By contrast, inflamed organs of mice lacking lymphotoxin-[alpha] or its receptor did not accumulate the abnormal isoform PrP[superscript Sc], 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. |
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ISSN: | 0036-8075 1095-9203 |
DOI: | 10.1126/science.1106460 |