Chronic schistosomiasis during pregnancy epigenetically reprograms T-cell differentiation in offspring of infected mothers

Eur J Immunol. 2017 May;47(5):841-847. doi: 10.1002/eji.201646836. Epub 2017 Apr 11.

Abstract

Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B-cell and T-cell development. Therefore, we focused our analyses on T-cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into TH 1 cells, whereas TH 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T-cell compartment affecting TH 2 and TH 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T-cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines.

Keywords: Epigenetic histone modification; In utero programming; Maternal helminth infection; Schistosomiasis; T-cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Differentiation*
  • Chronic Disease
  • Cytokines / genetics
  • Cytokines / immunology
  • Epigenesis, Genetic*
  • Female
  • Histones / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Lymphocyte Activation*
  • Mice
  • Mothers
  • Pregnancy
  • Pregnancy Complications, Parasitic / immunology*
  • Promoter Regions, Genetic
  • Schistosomiasis / immunology*
  • Schistosomiasis / parasitology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Th1 Cells / immunology
  • Th1 Cells / physiology
  • Th2 Cells / immunology
  • Th2 Cells / physiology

Substances

  • Cytokines
  • Histones
  • Interleukin-4