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

Infect Immun. 2013 Jul;81(7):2546-53. doi: 10.1128/IAI.01047-12. Epub 2013 May 6.

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 worms from a challenge infection was delayed in selenium (Se)-deficient mice. In order to explore mechanisms associated with the delayed expulsion, 3-week-old female BALB/c mice were placed on a torula yeast-based diet with or without 0.2 ppm Se, and after 5 weeks, they were inoculated with H. bakeri infective third-stage larvae (L3s). Two weeks after inoculation, the mice were treated with an anthelmintic and then rested, reinoculated with L3s, and evaluated at various times after reinoculation. 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 that in 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 suboptimal Se-dependent local immune response. Notably, the process of worm expulsion was restored within 2 to 4 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-β protein, anti-H. bakeri IgG1 production, and reduced worm fecundity and ATP-dependent metabolic activity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Anthelmintics / pharmacology
  • Enzyme Activation
  • Female
  • Fertility
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / metabolism
  • Heligmosomatoidea / immunology*
  • Heligmosomatoidea / pathogenicity
  • Immunity, Cellular / drug effects*
  • Intestine, Small / drug effects
  • Intestine, Small / immunology
  • Larva / immunology
  • Larva / pathogenicity
  • Mice
  • Mice, Inbred BALB C
  • Selenium / deficiency*
  • Selenium / pharmacology
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Time Factors

Substances

  • Anthelmintics
  • Adenosine Triphosphate
  • Glutathione Peroxidase
  • Selenium