<p>In response to an enteric infection, the host mobilizes inflammatory and immune cells to combat the invading pathogen. Studies suggest that physiologic tissues such as smooth muscle are also recruited to aid in host defense, and that this recruitment depends on the hosts immune response. The purpose of this thesis was to use the intestinal phase of a primary Trichinella spiralis infection in mice to study the accompanying changes in smooth muscle contraction, including their role in host defense and their immunological basis. Naive mice were infected with the nematode parasite T. spiralis . Infection caused a significant increase in intestinal longitudinal muscle contraction in response to carbachol in vitro . Testing several mouse strains, we found that the strains that developed the greatest increases in muscle contraction also expelled the infection the most rapidly. Two phases of increased contraction were identified, the early phase when muscle contraction first increases, and the persistent phase, when the increased muscle tension was sustained until at least day 21 post-infection. We also found that infected mice lacking T cells, and specifically CD4 +ve T cells, exhibited an attenuated increase in both phases of muscle contraction. We also tested the role of the Th2 cytokines, interleukins 4 and 5, which are produced by CD4 +ve T cells during a nematode infection. We found that during infection, IL-5 deficient mice developed a normal early phase of increased muscle contraction, but were significantly impaired in the persistent muscle response. We also examined the role of IL-4, through gene transfer. Following surgery, we infected the intestinal surface with either control adenoviral vectors, or a virus encoding the cytokine IL-4. IL-4 overexpression significantly increased intestinal muscle contraction, while the control virus had no effect. In summary, my studies show that intestinal longitudinal muscle function is subject to immunomodulation, specifically by the actions of CD4 +ve T cells, and through the cytokine mediators IL-4 and 5.</p> / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/6634 |
| Date | 12 1900 |
| Creators | Vallance, Andrew Bruce |
| Contributors | Collins, Stephen M., Medical Sciences |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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