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Journal of Virology, February 2005, p. 1888-1897, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1888-1897.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells

Joanne Mohan, Moira E. Bruce, and Neil A. Mabbott^*

Neuropathogenesis Unit, Institute for Animal Health, Edinburgh, Scotland, United Kingdom

Received 18 June 2004/ Accepted 7 September 2004

Many natural transmissible spongiform encephalopathy (TSE) infections are likely to be acquired peripherally, and studies in mice show that skin scarification is an effective means of scrapie transmission. After peripheral exposure, TSE agents usually accumulate in lymphoid tissues before spreading to the brain. The mechanisms of TSE transport to lymphoid tissues are not known. Langerhans cells (LCs) reside in the epidermis and migrate to the draining lymph node after encountering antigen. To investigate the potential role of LCs in scrapie transportation from the skin, we utilized mouse models in which their migration was blocked either due to CD40 ligand deficiency (CD40L^–/– mice) or after caspase-1 inhibition. We show that the early accumulation of scrapie infectivity in the draining lymph node and subsequent neuroinvasion was not impaired in mice with blocked LC migration. Thus, LCs are not involved in TSE transport from the skin. After intracerebral inoculation with scrapie, wild-type mice and CD40L^–/– mice develop clinical disease with similar incubation periods. However, after inoculation via skin scarification CD40L^–/– mice develop disease significantly earlier than do wild-type mice. The shorter incubation period in CD40L^–/– mice is unexpected and suggests that a CD40L-dependent mechanism is involved in impeding scrapie pathogenesis. In vitro studies demonstrated that LCs have the potential to acquire and degrade protease-resistant prion protein, which is thought to be a component of the infectious agent. Taken together, these data suggest that LCs are not involved in scrapie transport to draining lymphoid tissues but might have the potential to degrade scrapie in the skin.

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* Corresponding author. Mailing address: Institute for Animal Health, Neuropathogenesis Unit, Ogston Bldg., West Mains Rd., Edinburgh EH9 3JF, United Kingdom. Phone: 44(0)131-667-5204. Fax: 44(0)131-668-3872. E-mail: neil.mabbott{at}bbsrc.ac.uk.

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Journal of Virology, February 2005, p. 1888-1897, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1888-1897.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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