NR ARSA
AU Mohan,J.; Bruce,M.E.; Mabbott,N.A.
TI Follicular dendritic cell dedifferentiation reduces scrapie susceptibility following inoculation via the skin
QU Immunology 2005 Feb; 114(2): 225-34
PT journal article
AB Transmissible spongiform encephalopathies (TSEs) are a group of subacute infectious neurodegenerative diseases that are characterized by the accumulation in affected tissues of PrPsc, an abnormal isoform of the host prion protein (PrPc). Following peripheral exposure, TSE infectivity and PrPsc usually accumulate in lymphoid tissues prior to neuroinvasion. Studies in mice have shown that exposure through scarified skin is an effective means of TSE transmission. Following inoculation via the skin, a functional immune system is critical for the transmission of TSEs to the brain, but until now, it has not been known which components of the immune system are required for efficient neuroinvasion. Temporary dedifferentiation of follicular dendritic cells (FDCs) by treatment with an inhibitor of the lymphotoxin-beta receptor signalling pathway (LTßR-Ig) 3 days before or 14 days after inoculation via the skin, blocked the early accumulation of PrPsc and TSE infectivity within the draining lymph node. Furthermore, in the temporary absence of FDCs before inoculation, disease susceptibility was reduced and survival time significantly extended. Treatment with LTßR-Ig 14 days after TSE inoculation also significantly extended the disease incubation period. However, treatment 42 days after inoculation did not affect disease susceptibility or survival time, suggesting that the infection may have already have spread to the nervous system. Together these data show that FDCs are essential for the accumulation of PrPsc and infectivity within lymphoid tissues and subsequent neuroinvasion following TSE exposure via the skin.
MH Animals; Dendritic Cells, Follicular/*immunology; Disease Susceptibility; Immunoblotting/methods; Immunoglobulin G/administration & dosage; Immunoglobulins, Fc/administration & dosage; Injections; Lymph Nodes/chemistry; Mice; Mice, Inbred BALB C; PrPsc Proteins/analysis; Receptors, Tumor Necrosis Factor/administration & dosage; Research Support, Non-U.S. Gov't; Scrapie/*immunology/*transmission; Skin/*immunology; Spleen/chemistry
AD Institute for Animal Health, Ogston Building, Edinburgh, United Kingdom.
SP englisch
PO England