Award details

Identifying the key events in TSE agent neuroinvasion via lymphoid tissues

Reference	BBS/E/A/00001660
Principal Investigator / Supervisor	Professor Neil Mabbott
Co-Investigators / Co-Supervisors
Institution	The Roslin Institute
Department	The Roslin Institute Department
Funding type	Research
Value (£)	158,381
Status	Completed
Type	Institute Project
Start date	01/04/2007
End date	31/03/2010
Duration	36 months

Abstract

Many TSE infections arise most often from peripheral exposure to infection. Following exposure the TSE agent accumulates first upon follicular dendritic cells (FDCs) in lymphoid tissues such as the Peyer¿s patches or draining lymph nodes. This early accumulation in lymphoid tissues is critical as neuroinvasion is blocked in the absence of FDCs or the draining lymphoid tissue. How the TSE agent first reaches the draining lymphoid tissue is not known. Our research has demonstrated that complement plays an important role in the localization of TSE infectivity to FDCs, but whether migratory cells transport TSE agents is not known. We aim to determine the cellular mechanisms involved in the delivery of TSE agents from the skin to the draining lymphoid tissue. An in vitro system will be developed to address how FDCs acquire and process TSE agents. Important issues to be determined include: how do TSE agents interact with FDCs? Why do only some TSE agents interact with TSE agents? How are TSE agents delivered to FDCs? How are TSE agents disseminated from FDCs? Do FDCs release exosomes? Are TSE agents released from FDCs via exosomes? Does TSE infection impair the function of FDCs? Is FDC phenotype modified following exposure to TSE agents? Recent studies suggest that inflammation may affect TSE pathogenesis either by enhancing agent uptake from mucosal sites, or expanding their tissue distribution. Isolated lymphoid follicles (ILFs) are recently identified lymphoid structures distributed throughout the intestine of rodents with features similar to Peyer¿s patches. The number and maturation status of ILFs can be modulated by the microbiological or inflammatory status of the intestine. Thus these factors might dramatically enhance TSE susceptibility due to and increased number of FDC-containing mature ILFs. In this project mouse models will be used to determine the involvement of mature ILFs in TSE agent neuroinvasion from the intestine.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Immunology, Neuroscience and Behaviour, 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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