Submitted to: International Journal for Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/7/2006
Publication Date: 5/24/2006
Citation: Kringel, H., Iburg, T., Dawson, H.D., Aasted, B., Roepstorff, A. 2006. A time course study of immunological responses in trichuris suis infected pigs. International Journal for Parasitology. 36(8):915-924. Interpretive Summary: More than 1 billion people worldwide are infected with whipworm (Trichuris trichiura). Morbidity worldwide is comparable to that of tuberculosis and expressed primarily in children as malnutrition, poor growth and impaired cognitive development. No vaccine is available and drug treatment is difficult to apply in underdeveloped areas where the disease is a problem. It is notable that the immune response to worms is striking similarity to expression of allergic disease. Mouse models exist to study this disease, but the response in pigs is of economic importance and it is also more representative of infections in humans. We have defined a targeted assessment of genes that contribute to immunity to Trichuris in pigs. Pigs were infected with Trichuris suis and intestinal immunity was assessed by gene expression profiling every other week from 1 to 11 weeks post inoculation. Genes were chosen to represent a panel of markers for human allergy and asthma. A localized gene-expression pattern gradually developed in the colon and draining lymph node of infected pigs that mimicked expression of an allergic response. These results expand our knowledge of the intestinal immune response to Trichuris, describe genes that regulate resistance, and provide baseline data to monitor future studies of the interaction between micronutrients such as vitamin A and susceptibility to parasitic and allergic diseases. This work will be important to both animal scientists and nutritionists that explore the role of nutrition in immunity.
Technical Abstract: In order to investigate immunological changes over time in pigs infected with Trichuris suis, we inoculated 40 pigs with 5,000 infective T. suis eggs and left 40 pigs as uninfected controls. Equal numbers of pigs from both groups were sacrificed every other week from 1 to 11 weeks post inoculation (p.i.). At necropsy tissue samples were collected from all pigs and their worm burdens were determined. In the proximal colon of T. suis infected pigs infiltration of eosinophils peaked 5 weeks p.i. and mast cell infiltration developed from 5 to 11 weeks p.i.. Histological evaluation of the proximal colon revealed that the presence of T. suis was closely associated with intestinal histopathological changes such as crypt and goblet cell hyperplasia and hypertrophy of the mucosa. The crypt lengths were positively associated with worm burdens. Real-time PCR analysis of genes related to immune function indicate a local increased expression of genes coding for CCR3, ARG1, MUC5AC, IL-4, IL-5, IL-13, Fc epsilon R1 alpha, and IL-13R alpha 2 and decreased expression of genes coding for iNOS, TNF-alpha, IL-10, CD3 epsilon, CD80, CD86, IL-4R alpha, IL-13R alpha 1 and CD40 in the proximal colon of pigs infected with T. suis. This local Type 2-like gene-expression pattern indicates that the Type 2 immune response characteristic of helminth infections in both mouse and man also develops in pigs infected with T. suis. The results from this study expand our knowledge of the immunomodulatory effect of T. suis and allow for further understanding of the mechanisms underlying the positive effect of treating inflammatory bowel disease patients with T. suis eggs. 12/23/05