Award details

Determining the mechanisms of TSE agent delivery from the skin to lymphoid tissues

Reference	BBS/E/R/00001822
Principal Investigator / Supervisor	Professor Neil Mabbott
Co-Investigators / Co-Supervisors
Institution	The Roslin Institute
Department	The Roslin Institute Department
Funding type	Research
Value (£)	3,225
Status	Completed
Type	Institute Project
Start date	03/10/2007
End date	02/10/2011
Duration	48 months

Abstract

Natural TSE infections are likely to be acquired orally, other routes of TSE transmission have been identified eg skin scarification. Some natural TSE cases might be transmitted through skin lesions during close contact, during the birth process or through damage to oral mucosa after consumption of coarse feed. Following inoculation via the skin the spread of disease to the CNS does not occur by direct uptake by nerves in the skin. Instead, TSE agents accumulate first upon follicular dendritic cells (FDCs) within lymphoid tissues by a process which is unknown. Treatments that block TSE agent accumulation in lymphoid tissues may have therapeutic potential against peripherally-acquired TSE agents. Therefore, identification of the cells involved in TSE transport may identify an important therapeutic target. Our data indicate that the TSE agent reaches the draining lymph node via the lymph, and several cells have the potential to capture TSE agents within the skin and deliver them to the draining lymph node. The aim of this study is to determine the mechanism/s through which this occurs. Migratory haematopoietic dendritic cells (DCs) are a distinct lineage from tissue-fixed, stromal-derived, FDCs. DCs continually circulate throughout the host sampling antigens and delivering them to lymphoid nodes. Macrophages, in contrast, appear to destroy TSE agents making them an unlikely transport candidate. Skin-derived DCs can acquire the TSE agent in vitro, but direct demonstration of their involvement in disease pathogenesis is lacking. Therefore this study will utilise transgenic mice lines with specific depletion of skin DC subsets to test the hypothesis that if a specific cell population plays an important role in TSE agent transportation from the skin, their depletion will block or impair agent delivery to the draining lymph node and delay/prevent the onset of clinical TSE disease.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Immunology, TSEs (transmissible spongiform encephalopathies)
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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