Investigation the immunological response elicited to the gastrointestinal nematode pinworm (Syphacia obvelata)
Doctoral Thesis
2006
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University of Cape Town
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It is important to emphasize with the advance of biotechnology and increased global exchange of animals and animal products, the risks of introducing adventitious infections. Previous studies of specitic-pathogen-free mouse colonies have identified the presence of infectious agents in 10-35% of research institutions investigated. Prevalence was higher among non-SPF mice with pinworm reported in 70% of institutions housing rodents under these conditions. Pinworm, a gastrointestinal (GI) nematode is commonly found in laboratory animals. The direct transmission of the parasite by contaminated food, water and bedding result in their continual re-exposure to the host, making the control of pinworm in animal holdings quite difficult. Syphacia obvelata, mouse pinworm, has been shown to interfere with research goals in several experimental models. In this study, we show the consequence of a pinworm outbreak in a transgenic barrier facility and define the immune response elicited in BALB/c mice. Infection with S. obvelata induced a transient Th2-type immune response with elevated cytokine production and parasite-specific IgG1. In contrast, HALB/c mice, deficient for IL-13, lL-4/13 or IL-4Ra showed chronic disease with more than 100-fold higher parasite burden, increased IFN-y production, parasite-specific IgG2b and a default Th2 response. Notably, infected lL-4-/- BALB/c mice showed only slight elevated parasite burden compared to controls, suggesting that IL-13 plays the dominant role in the control of S. obvelata. Furthermore, no significant eosinophilia, mastocytosis or goblet cell hyperplasia was induced. In a well-established ovalbumin (Ova) anaphylaxis model, we show that mice infected with S. obvelata induce a more severe anaphylactic reaction, with consistently greater temperature decline than their non-infected counterparts. Analysis of spleen cells further revealed a marked reduction of Ova-specific Th2 cytokines, highlighting the importance of pinworm free experimental mice. Finally, we generated anti-S. obvelata antibody to optimize the detection ELISA and identified target epitopes for future analysis. In conclusion, we identify the T helper immune response induced to S. obvelata and demonstrate the importance of IL-13 for the expulsion of the GI nematode. We show that S. obvelata induces a non-protective immune response to a common food allergen and confirm that the pinworm-specific ELISA is an effective diagnostic tool for detecting pinworm infected mice.
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Michels, C. 2006. Investigation the immunological response elicited to the gastrointestinal nematode pinworm (Syphacia obvelata). University of Cape Town.