Award details

The role of lymphoid tissues in TSE pathogenesis

Reference	BBS/E/I/00001071
Principal Investigator / Supervisor	Professor Neil Mabbott
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	7,151
Status	Completed
Type	Institute Project
Start date	01/10/2003
End date	30/09/2006
Duration	36 months

Abstract

Transmissible spongiform encephalopathies (TSEs), such as scrapie, BSE and variant CJD are chronic degenerative diseases of the central nervous system (CNS). Natural or accidental TSE infections arise most often from peripheral infection (eg: ingestion) in which case infectivity accumulates in lymhoid tissues before spreading to the CNS. Our studies of mouse scrapie models have shown that follicular dendritic cells are critical for scrapie accumulation in lymphoid tissues and subsequent neuroinvasion [1,2]. The early peripheral phase of TSE pathogenesis within lymphoid tissues offers an early opportunity for intervention following peripheral exposure by preventing the spread of disease to the CNS. Therefore, a thorough understanding of TSE pathogenesis in the periphery is fundamental for the development of practical intervention strategies. The role of individual draining lymphoid tissues in TSE pathogenesis is not known. During embryonic development cytokines provide essential signals for the development of secondary lymphoid tissue [3]. Inhibition of lymphotoxin (LT)-signaling during gestation disrupts lymph node and Peyer¿s patch development in the embryo. Lymphotoxin ?-deficient mice lack most lymph nodes and almost all Peyer¿s patches. In contrast, mice deficient in LT? retain mesenteric and cervical lymph nodes, but lack all other lymph nodes. In this project, the contribution of particular lymphoid tissues to susceptibility to TSE agents will be investigated. To achieve this, the following approach will be used. Briefly, TSE pathogenesis will be investigated in mice where specific lymph node development was prevented. These mice will then be inoculated with TSE agents by one of various peripheral routes.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
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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