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Follicular dendritic cell dedifferentiation reduces scrapie susceptibility following inoculation via the skin
Author(s) -
Mohan Joanne,
Bruce Moira E.,
Mabbott Neil A.
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.02074.x
Subject(s) - infectivity , scrapie , biology , immune system , follicular dendritic cells , inoculation , virology , gliosis , incubation period , immunology , incubation , disease , virus , pathology , t cell , prion protein , medicine , neuroscience , antigen presenting cell , biochemistry
Summary Transmissible spongiform encephalopathies (TSEs) are a group of subacute 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, TSE infectivity and PrP Sc 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‐β receptor signalling pathway (LTβR‐Ig) 3 days before or 14 days after inoculation via the skin, blocked the early accumulation of PrP Sc 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 LTβR‐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 PrP Sc and infectivity within lymphoid tissues and subsequent neuroinvasion following TSE exposure via the skin.