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Mechanisms of transmission of TSE agents from the intestine to lymphoid tissues

Reference	BS308133
Principal Investigator / Supervisor	Dr Gordon MacPherson
Co-Investigators / Co-Supervisors	Dr Moira Bruce, Mrs Christine Farquhar, Professor Neil Mabbott
Institution	University of Oxford
Department	Sir William Dunn Sch of Pathology
Funding type	Research
Value (£)	370,256
Status	Completed
Type	Research Grant
Start date	01/11/1997
End date	01/11/2000
Duration	36 months

Abstract

Natural infection with TSE agents (TSEA) is largely via the oral route. After oral infection with scrapie, infectivity is found first in Peyer's patches (PP) and in lymph nodes and spleen before the CNS. Migration of TSEA to the CNS appears to be dependent on follicular dendritic cells in lymphoid organs. Intraintestinal protein is translocated to PP and is taken up by dendritic cells which then migrate to mesenteric nodes. We suggest that TSEA are similarly translocated and may be captured by DC. To test this scrapie agent will be given to mesenteric-lymphadenectomized rats by gavage and DC, lymphocytes and plasma separated from intestinal pseudo-afferent lymph. PP will be excised from rats after infection and lymphocytes, DC and macrophages separated. To detect PrP, cells will be examined by immunocytochemistry ad cells and plasma tested by intracerebral injection into mice. We will use a mannose-receptor fusion protein to isolate putative antigen-transporting cells from nodes after intestinal infection and test them as above. We will use a ligand binding assay to assess the ability of different cells to bind PrP. We will attempt to inhibit binding with antibodies to different surface molecules on DC and other cells. We will determine accessibility of antigen to DC, FDC and macrophages in PP and mesenteric nodes by injecting antibodies that bind to these cells and using double labelling to determine their localisation. These experiments will help define mechanisms of pathogenesis of TSE after oral infection.

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	Biology of Spongiform Encephalopathies - Phase 3 (BS3) [1996-1997]
Funding Scheme	X – not Funded via a specific Funding Scheme

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