Migrating intestinal dendritic cells transport PrP(Sc) from the gut.
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.
Huang
Fang-Ping
FP
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK1.
Farquhar
Christine F
CF
Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK2.
Mabbott
Neil A
NA
Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK2.
Bruce
Moira E
ME
Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK2.
MacPherson
G Gordon
GG
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK1.
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D018620:PrPSc Proteins / Q000378:metabolism*; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism
D018620:PrPSc Proteins