Factors influencing the development of protective and pathological responses to Trichinella spiralis infection
This thesis confirms the importance of Th2 responses in the development of protective and pathological responses to T. spiralis infection and shows that the role of IL-4 in the development of enteropathy depends on host mouse strain. Conversely a role in Th2 cytokine signalling to cells of the macrophage/neutrophil lineage in limiting enteropathy was also demonstrated. This thesis also demonstrated that co-stimulation via ICOS and OX40 can modulate the development of Th2 responses and the development of T. spiralis induced enteropathy and mastocytosis. The failure of TNFα/LTα -/- mice to expel T. spiralis from the small intestine despite developing a more severe enteropathy, this suggests that TNFα or LTα may play important protective roles in both expulsion and in limiting enteropathy. TNFα/LTα -/- mice also failed to develop mucosal mastocytosis suggesting that enteropathy in these mice is mast cell independent. It was also shown that signalling via the novel receptor PAR-2 plays a role in the development of enteropathy but not in the expulsion of T. spiralis, and was not required for the development of mucosal mastocytosis but enhanced mast cell degranulation. Thus, in conclusion this thesis provides further evidence that the expulsion of T. spiralis is not a direct result of the development of enteropathy and that different mechanisms are responsible for parasite expulsion and the development of enteropathy.