Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis

Abstract

The rat tapeworm Hymenolepis diminuta was used to test the hypothesis that helminth infection could modulate murine colitis. Mice were infected with five H. diminuta cysticercoids, and colitis was evoked via free access to 4% (wt/vol) dextran sulfate sodium (DSS)-containing drinking water for 5 days. BALB/c mice were either infected with H. diminuta and 7 days later exposed to DSS (prophylactic strategy) or started on DSS and infected with H. diminuta 48 h later (treatment strategy). Naive and H. diminuta-only-infected mice served as controls. On autopsy, colonic segments were processed for histological examination and myeloperoxidase (MPO) measurement or mounted in Ussing chambers for assessment of epithelial ion transport. Cytokines (gamma interferon [IFN-gamma], interleukin 12 [IL-12], and IL-10) were measured in serum and colonic tissue homogenates. DSS treatment resulted in reduced ion responses (indicated by short-circuit current [Isc]) to electrical nerve stimulation, the cholinergic agonist carbachol, and the adenylate cyclase activator forskolin compared to controls. H. diminuta infection, either prophylactic or therapeutic, caused a significant (P < 0.05) amelioration of these DSS-induced irregularities in stimulated ion transport. In contrast, the histopathology (i.e., mixed immune cell infiltrate, edema, and ulcerative damage) and elevated MPO levels that accompany DSS colitis were unaffected by concomitant H. diminuta infection. Similarly, there were no significant differences in levels of IFN-gamma, IL-12, or IL-10 in serum or tissue from any of the treatment groups at the time of autopsy. We suggest that abolishment of colitis-induced epithelial ion transport abnormalities by H. diminuta infection provides proof-of-principle data and speculate that helminth therapy may provide relief of disease symptoms in colitis.

FIG. 1

Change in Isc in colonic tissue in response to EFS. Mice were infected with five cysticercoids of H. diminuta with or without a subsequent 5-day exposure to 4% (wt/vol) DSS-containing drinking water (means ± SEM; ∗, P < 0.05 compared to control [con]; n = 7 or 8 mice from three separate experiments [prophylactic protocol]).

FIG. 2

(A) Change in Isc in colonic tissue in response to CCh (10⁻⁴ M). Mice were infected with five cysticercoids of H. diminuta with or without a subsequent 5-day exposure to 4% (wt/vol) DSS-containing drinking water (a negative value indicates a drop in Isc; means ± SEM; ∗ and #, P < 0.05 compared to other groups; n = 7 or 8 mice from three separate experiments). (B) Four representative Isc responses to CCh (arrow): a, control; b, H. diminuta infection; c, 4% DSS treatment; d, H. diminuta plus DSS (prophylactic protocol).

FIG. 3

Colonic histologic damage scores (∗, P < 0.05 compared to control [con]; n = 7 or 8 mice from three separate experiments [prophylactic protocol]; see the legend to Fig. 1).

FIG. 4

MPO levels in murine distal colonic segments (means ± SEM; ∗ and #, P < 0.05 compared to control [con]; n = 7 or 8 mice from three separate experiments [prophylactic protocol]; see the legend to Fig. 1).

FIG. 5

Change in murine Isc in response to EFS, CCh (10⁻⁴ M), and FSK (10⁻⁵ M). Mice were started on 4% DSS and then infected with H. diminuta (means ± SEM; ∗ and #, P < 0.05 compared to other groups; n = 4 to 8 mice from three separate experiments [treatment protocol]).