Haemonchus contortus infection : investigation of rejection mechanisms in resistant sheep

Infection with Haemonchus contortus is a serious disease of livestock, particularly sheep in both Australia and around the world, and results in production loss and quite often death. However the interaction between H. contortus and the host remains poorly understood. To develop better protection and prevention strategies, further understanding of the host-parasite relationship is required. In this thesis the host response to H. contortus infection was examined with particular focus on immunological mechanisms by which resistant sheep can reject or kill incoming larvae. Contrasting resistance mechanisms were identified based on cellular and molecular profiles in the abomasal mucosa after differing H. contortus immunisation protocols. The data suggest that there are at least two different immune-based mechanisms utilised by the host to reject or kill incoming larvae. Depending on the immunisation protocol, resistant sheep could mount either a delayed rejection response likely based on mucosal eosinophils, or a rapid rejection response based on mucosal mast cells and globule leucocytes. The delayed rejection response showed a clear type II immune bias with mucosal upregulation of interleukin (IL) -4, 5, 13 and galectin-15 mRNA and protein following larval challenge. In contrast, sheep able to rapidly reject H. contortus larvae showed a marked abomasal mucosal mast cell, globule leucocyte and intraepithelial lymphocyte hyperplasia. This was confirmed by an ex vivo tissue explant model showing that resistant sheep with abomasal mucosal mast cell/ globule leucocyte hyperplasia could reject larvae using an immediate hypersensitivity mechanism. Characterisation of intraepithelial lymphocytes in resistant sheep also suggests that these cells may play an important role in the rapid rejection response. In conclusion, this thesis has examined different aspects of H. contortus larval rejection in sheep after hyperimmunisation and has shown some promising results that strongly suggest there are at least two different immunological mechanisms of H. contortus rejection. The foundations of both an in vivo and ex vivo model of H. contortus infection for use in further research on multiple mechanisms of host resistance to H. contortus have been established, and will provide valuable tools for investigation of these complex areas in both an experimental and field setting.