Recent studies showed that enteric helminth
infection improved symptoms in patients with
inflammatory bowel disease as well as in experimental models of
colitis. The aim of this study was to determine the mechanism of the protective effect of helminth
infection on
colitis-induced changes in immune and epithelial cell function. BALB/c mice received an oral
infection of Heligmosomoides polygyrus third-stage larvae, were given intrarectal saline or trinitrobenzene
sulfonic acid (TNBS) on day 10 postinfection, and were studied 4 days later. Separate groups of mice received intrarectal saline or TNBS on day 10 and were studied on day 14. Muscle-free colonic mucosae were mounted in Ussing chambers to measure mucosal permeability and secretion. Expression of
cytokines was assessed by quantitative real-time PCR, and mast cells were visualized by immunohistochemistry. TNBS-induced
colitis induced mucosal damage, upregulated Th1
cytokines, and depressed secretory responses. Heligmosomoides polygyrus elevated Th2
cytokine expression, increased mast cell infiltration and mucosal resistance, and also reduced some secretory responses. Prior H. polygyrus
infection prevented TNBS-induced upregulation of Th1
cytokines and normalized secretory responses to specific agonists. TNBS-induced
colitis did not alter H. polygyrus-induced mast cell infiltration or upregulation of Th2
cytokine expression. The results indicate that the protective mechanism of enteric
nematode infection against TNBS-induced
colitis involves prevention of Th1
cytokine expression and improved colonic function by a mechanism that may involve mast cell-mediated protection of neural control of secretory function. Similar response patterns could account for the clinical improvement seen in
inflammatory bowel disease with
helminthic therapy.