Selenium status alters the immune response and expulsion of adult Heligmosomodies bakeri in mice

Authors: Smith, Allen; Cheung, Lumei; SHEA-DONOHUE, TEREZ - University Of Maryland; Urban, Joseph

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2013
Publication Date: 7/1/2013
Citation: Smith, A.D., Cheung, L., Shea-Donohue, T., Urban Jr, J.F. 2013. Selenium status alters the immune response and expulsion of adult Heligmosomodies bakeri in mice. Infection and Immunity. 81(7):2546-2553.

Interpretive Summary: Heligmosomoides bakeri (Hb) is a parasitic worm that inhabits the small intestine of infected mice and induces a potent immune response that mimics the response seen in humans with worm infection and suffering from allergy and asthma related diseases. In this study we investigated how the nutrient selenium affected the ability of mice to clear the worm infection and to elucidate a mechanism of action. Mice were made deficient in selenium by removal from the diet and then infected with Hb. The adult worms are not expelled from the intestine of selenium deficient mice but are in mice fed a selenium adquate diet. The immune response in the intestine (site of infection) was decreased in selenium deficient mice. Feeding selenium deficient mice a selenium adequate diet quickly restored immune function to expel the worms. It also restored protective immune pathways and oxidative enzyme activity in the small intestine. Thus, adequate levels of selenium in the diet are required for optimal immune function in the small intestine and resistance to worm infections. These results also suggest that selenium may be important in controlling immune responses associated with allergy and asthma.

Technical Abstract: Heligmosomoides bakeri is a nematode with parasitic development exclusively in the small intestine of infected mice that induces a potent STAT6-dependent Th2 immune response. We previously demonstrated that host protective expulsion of adult H. bakeri was delayed in selenium (Se) deficient mice. In order to explore mechanisms associated with the delayed expulsion, three-week old female Balb/c mice were placed on a Torula yeast-based diet with or without 0.2 ppm Se, and inoculated five weeks later with H. bakeri infective third-stage larvae (L3), anthelmintic-treated two weeks later, rested, re-inoculated with L3, and evaluated at various times after inoculation. Analysis of gene expression in parasite-induced cysts and surrounding tissue isolated from the intestine of infected mice showed that the local tissue Th2 response was decreased in Se deficient mice compared to Se adequate mice. In addition, adult worms recovered from Se deficient mice had higher ATP levels than worms from Se adequate mice indicating greater metabolic activity in the face of a sub-optimal Se-dependent local immune response. Notably, the process of worm expulsion was restored within two to four days after feeding a Se-adequate diet to Se-deficient mice. Expulsion was associated with an increased local expression of Th2- associated genes in the small intestine, intestinal glutathione peroxidase activity, secreted Relm-beta protein, reduced worm fecundity, and ATP-dependent metabolic activity.