Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion

PLoS Pathog. 2021 Feb 1;17(2):e1009260. doi: 10.1371/journal.ppat.1009260. eCollection 2021 Feb.


Epidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offspring immunity, as well as immunity induced by a commercial tetanus/diphtheria vaccine using a dual IL-4 reporter mouse model of maternal schistosomiasis. We demonstrate that offspring born to S. mansoni infected mothers have reduced circulating plasma cells and peripheral lymph node follicular dendritic cells at steady state. These reductions correlate with reduced production of IL-4 by iNKT cells, the cellular source of IL-4 in the peripheral lymph node during early life. These defects in follicular dendritic cells and IL-4 production were maintained long-term with reduced secretion of IL-4 in the germinal center and reduced generation of TFH, memory B, and memory T cells in response to immunization with tetanus/diphtheria. Using single-cell RNASeq following tetanus/diphtheria immunization of offspring, we identified a defect in cell-cycle and cell-proliferation pathways in addition to a reduction in Ebf-1, a key B-cell transcription factor, in the majority of follicular B cells. These reductions are dependent on the presence of egg antigens in the mother, as offspring born to single-sex infected mothers do not have these transcriptional defects. These data indicate that maternal schistosomiasis leads to long-term defects in antigen-induced cellular immunity, and for the first time provide key mechanistic insight into the factors regulating reduced immunity in offspring born to S. mansoni infected mothers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / immunology
  • B-Lymphocytes / immunology*
  • Diphtheria-Tetanus Vaccine / immunology
  • Female
  • Immunologic Memory
  • Interleukin-4 / immunology*
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Natural Killer T-Cells / immunology
  • Pregnancy
  • Pregnancy Complications, Parasitic / immunology*
  • Prenatal Exposure Delayed Effects / immunology
  • Prenatal Exposure Delayed Effects / parasitology
  • RNA-Seq
  • Schistosomiasis mansoni / immunology*
  • Stromal Cells / immunology


  • Diphtheria-Tetanus Vaccine
  • Interleukin-4