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Title: Helminth infections in animals and man: Population dynamics, host susceptibility and immuno-modeulatory effects

Author
item KRINGEL, HELENE - DANISH CTR PARASITOL
item Dawson, Harry
item Urban, Joseph
item ROEPSTORFF, ALLAN - DANISH CTR PARASITOL

Submitted to: Symposium Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 6/15/2005
Publication Date: 8/15/2005
Citation: Kringel, H., Dawson, H.D., Urban Jr, J.F., Roepstorff, A. 2005. Helminth infections in animals and man: Population dynamics, host susceptibility and immuno-modeulatory effects. Proceedings of the Abildgaard Symposium. University of Life Sciences. Danish Centre for Experimental Parasitology. pp. 65-72.

Interpretive Summary: Immunity to nematode parasites is characterized by an immediate type hypersensitivity reaction that can expel worms from the intestine with minimal effects on the equilibrium of the host. A number of studies in both mice and humans have demonstrated that nematode parasite infection can ameliorate the severe inflammatory responses in the intestine that appear spontaneously or that are induced by microbial agents. Eggs from the pig whipworm Trichuris suis, in fact, have been used to treat people with Crohn’s disease and ulcerative colitis with observed improvements in their clinical scores. It is important, however, to better understand the dynamics and mechanism of action of this response in the intestine since worm infections can also have harmful consequences under certain circumstances. The pig is the natural host of Trichuris suis and also represents a model for infection that is closer to humans than that in mice. Nevertheless, studies in mice can be used as a guide to plan hypotheses for testing in large animal models. The current review presents information on the localized tissue response in the pig colon and the gene expression patterns for immune-related cytokines that are associated with Trichuris infection. The pattern of the response is generally similar to what has been observed in mice and suggests that the infection induces several cytokines with anti-inflammatory properties that could explain the benefit of infection on IBD in humans. Scientists and clinicians interested in these infectious agents and control of disease severity will benefit from this information.

Technical Abstract: Whipworm infections with the two closely related species, Trichuris trichiura and Trichuris suis are common in human and pigs, respectively. The intestinal anatomy and physiology and immune function of the two hosts are similar and we considered pigs a very useful model for human infections. In mouse models it is well established that T. muris induces a protective Th2-associated immune response, but one must be careful extrapolating results obtained from inbred mouse strains to the human host. Studying human trichuriasis by controlled experimental infections with T. suis in out-bred pigs overcomes many of the limitations of mice. In addition, increased attention on the immunomodulatory effect of parasites and in particular the promising results from using T. suis eggs for treating inflammatory bowel disease (IBD) have augmented the importance of understanding the immune response against this parasite of swine. With this purpose in mind, we infected pigs with T. suis and evaluated several immune responses over time as well as expression of an array of genes related to immune function in different tissues. We found T. suis infections to be associated with eosinophilia, basophilia, mastocytosis, colon crypt hyperplasia and colon mucosa hypertrophy; and real-time PCFR analysis revealed a local Th2-like gene expression pattern. The results support the current hypothesis of a Th2-skewed response to Trichuris obtained from the mouse model and contribute to the limited knowledge on the mechanisms underlying the positive effect of treating IBD patients with T. suis eggs.