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Title: The interaction of bovine antigen-presenting-cells with foot-and-mouth disease virus
Author: Robinson, Lucy
ISNI:       0000 0001 3528 7652
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2008
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Foot-and-mouth disease virus (FMDV) causes an acute vesicular disease affecting over 70 animal species, including cattle and pigs. Foot-and-mouth disease (FMD) is a global problem, resulting in significant economic losses and human suffering. Currently vaccination is the only control measure available for endemic countries, but this strategy has a number ofshortcomings and the development of improved vaccines is limited by our understanding ofthe immune response to the disease. The effective induction of protective immunity is mediated by host dendritic cells (DC). These cells are unique in their ability to control not only the magnitude, but the character of the immune response in order to mediate effective clearance of pathogens, but their role in FMDV infection is uncharacterised. This study aimed to advance understanding ofthe interaction between bovine DC and FMDV. Monocyte-derived DC (moDC) were exposed to both wild-type (integrinbinding) and tissue culture adapted (heparan sulphate binding) isolates of FMDV in vitro. MoDC were not susceptible to infection by wild-type virus, but were susceptible to culture-adapted FMDV. The binding ofspecific antibodies to wild-type FMDV allowed significantly enhanced infection, which occurred in the absence of complement components, and required CD32 (FcyR). Infection of moDC by FMDV immune complexes (IC) resulted in high levels of cell death, and impaired memory CD4+ T-cell stimulation. However, exposing moDC to immune complexes containing inactivated FMDV resulted in significantly increased stimulation ofmemory T-cells. Although DC are the professional antigen presenting cell type, monocytes and macrophages share a common lineage with these cells and are also important in immunity to pathogens. Monocyte-derived macrophages shared FMDV infection characteristics with moDC. Monocytes however, were resistant to both FMDV and FMDV IC mediated infection despite expressing CD32. This was due to a specific defect in intemalisation of CD32 41 these cells, which was resolved upon their differentiation to moDC. The lack ofCD32 intemalisation was proposed to be linked to the absence of lipid rafts on the monocyte cell surface, which appear during their differentiation, concurrent with increased susceptibility to FMDV IC
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available