Investigation of markers associated with resistance to gastrointestinal nematode parasites in sheep

Gastrointestinal nematode (GIN) parasites of livestock pose a major economic burden on both developing and developed countries through disease resulting in production loss and animal death. Haemonchus contortus is the most pathogenic GIN parasite of small ruminants (sheep and goats) globally. Control primarily relies on indiscriminate anthelmintic treatment, however, due to anthelmintic resistance and the cost of drug development, this sole method of control is no longer viable. Integrated sustainable approaches are now required to effectively reduce the burden of H. contortus parasites on livestock production. Sustainable approaches include vaccination and breeding of GIN parasite resistant sheep, however, these approaches are limited by our lack of understanding of the host-parasite relationship. The aims of this thesis were twofold, the first involved providing a greater understanding of immune responses associated with protection and specifically focused on host galectins. This work identified sheep galectin-11 as a correlate of protection against a H. contortus experimental infection and demonstrated surface binding of endogenous and recombinant galectin-11 to larval and adult stages of H. contortus. In vitro experiments with recombinant galectin-11 inhibited larval exsheathment and growth providing evidence that reducing larval development may be an in vivo mechanism of galectin-11 production. The second aim of this thesis addressed whether host cutaneous hypersensitivity reactions could predict resistance (vaccine induced protection or natural resistance) to H. contortus infection. This study showed the ability of temperature and wheal responses of sheep to cutaneous larval injection to identify animals which had responded to a vaccination against H. contortus. However extension of this work showed that its ability to predict natural resistance in a small cohort of sheep was limited. In conclusion, this thesis has provided a greater understanding behind the release of host galectin-11 during infection and has identified cutaneous hypersensitivity reactions as a potential tool to measure immune responses induced by vaccination. Further genetic analysis relating to galectin-11 and cutaneous hypersensitivity reactions may lead to a greater understanding of the host-parasite interaction and become a source of new gene markers for GIN resistance for diagnostic development.