Scrapie transmission following exposure through the skin is dependent on follicular dendritic cells in lymphoid tissues.
BACKGROUND
Transmissible spongiform encephalopathies (TSEs) are chronic infectious neurodegenerative diseases that are characterized by the accumulation in affected tissues of PrP(Sc), an abnormal isoform of the host prion protein (PrP(c)). Following peripheral exposure, PrP(Sc) usually accumulates on follicular dendritic cells (FDCS) in lymphoid tissues before neuroinvasion. Studies in mice have shown that TSE exposure through scarified skin is an effective means of transmission. Following inoculation via the skin, a functional immune system is critical for the transmission of scrapie to the brain as severe combined immunodeficiency (SCID) mice are refractory to infection. Until now, it was not known which components of the immune system are required for efficient scrapie neuroinvasion following skin scarification.


OBJECTIVE
To determine which cells are critical for the transmission of scrapie to the brain following inoculation via the skin.


METHODS
A chimeric mouse model was used, which had a mismatch in PrP(c) expression between FDCs and other bone marrow-derived cells within lymphoid tissues. These chimeric mice were challenged with scrapie by skin scarification to allow the separate roles of FDCs and lymphocytes in peripheral scrapie pathogenesis to be determined.


RESULTS
We show that mature FDCs are essential for the accumulation of scrapie within lymphoid tissues and the subsequent transmission of infection to the brain following TSE exposure by this route. Furthermore, we show that the accumulation of PrP(Sc) and infectivity in the spleen is independent of PrP expression by lymphocytes or other bone marrow-derived cells.


CONCLUSIONS
Following inoculation with scrapie by skin scarification, replication in the spleen and subsequent neuroinvasion is critically dependent upon mature FDCs.
Mohan
Joanne
J
Institute for Animal Health, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK.
Brown
Karen L
KL
Farquhar
Christine F
CF
Bruce
Moira E
ME
Mabbott
Neil A
NA
D000818:Animals; D016026:Bone Marrow Transplantation; D001921:Brain / Q000378:metabolism; D002678:Chimera; D020566:Dendritic Cells, Follicular; D004198:Disease Susceptibility; D007136:Immunoglobulins / Q000378:metabolism; D008221:Lymphoid Tissue; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D018345:Mice, Knockout / Q000235:genetics; D016513:Mice, SCID; D018621:PrPC Proteins / Q000172:deficiency / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism; D012608:Scrapie / Q000635:transmission*; D012867:Skin; D013154:Spleen / Q000378:metabolism
D007136:Immunoglobulins; D018621:PrPC Proteins; D018620:PrPSc Proteins