Migrating intestinal dendritic cells transport PrPSc from the gut

• Published in: Journal of general virology Vol. 83; no. 1; pp. 267 - 271
• Main Authors: Huang, Fang-Ping, Farquhar, Christine F, Mabbott, Neil A, Bruce, Moira E, MacPherson, G. Gordon
• Format: Journal Article
• Language: English
• Published: Soc General Microbiol 01-01-2002
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-83-1-267

Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK 1
Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK 2
Author for correspondence: Gordon MacPherson. Fax [phone]. e-mail gordon.macpherson{at}path.ox.ac.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.