Journal of General Virology

Migrating intestinal dendritic cells transport PrP^Sc from the gut

Fang-Ping Huang,¹† Christine F. Farquhar,² Neil A. Mabbott,² Moira E. Bruce² and G. Gordon MacPherson¹

¹ Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK
² Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK

Bovine spongiform encephalopathy, variant Creutzfeldt–Jakob disease (vCJD) and possibly also sheep scrapie are orally acquired transmissible spongiform encephalopathies (TSEs). TSE agents usually replicate in lymphoid tissues before they spread into the central nervous system. In mouse TSE models PrP^c-expressing follicular dendritic cells (FDCs) resident in lymphoid germinal centres are essential for replication, and in their absence neuroinvasion is impaired. Disease associated forms of PrP (PrP^Sc), a biochemical marker for TSE infection, also accumulate on FDCs in the lymphoid tissues of patients with vCJD and sheep with natural scrapie. TSE transport mechanisms between gut lumen and germinal centres are unknown. Migratory bone marrow-derived dendritic cells (DCs), entering the intestinal wall from blood, sample antigens from the gut lumen and carry them to mesenteric lymph nodes. Here we show that DCs acquire PrP^Sc in vitro, and transport intestinally administered PrP^Sc directly into lymphoid tissues in vivo. These studies suggest that DCs are a cellular bridge between the gut lumen and the lymphoid TSE replicative machinery.

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© 2002 SGM

This article is now available in the January 2002 print issue of JGV (vol. 83, 267–271). The complete issue of the journal may be seen in electronic form on JGV Online.