CD4+CD25hiFOXP3+ cells in cord blood of neonates born from filaria infected mother are negatively associated with CD4+Tbet+ and CD4+RORγt+ T cells

PLoS One. 2014 Dec 22;9(12):e114630. doi: 10.1371/journal.pone.0114630. eCollection 2014.

Abstract

Background: Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses.

Methodology: Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3.

Results: No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively).

Conclusion: Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Female
  • Fetal Blood / cytology*
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Infant, Newborn
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Loa / growth & development
  • Loa / physiology
  • Mansonella / growth & development
  • Mansonella / physiology
  • Microfilariae / isolation & purification*
  • Mothers
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
  • Pregnancy
  • T-Box Domain Proteins / metabolism*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • T-Box Domain Proteins

Grants and funding

This work was supported by the EU-funded project the Immunological Interplay between Poverty Related Diseases and Helminth infections: An African-European Research Initiative “IDEA“ (HEALTH-F3-2009-241642) and the Deutsche Forschungsgemeinschaft-funded project Deutsch-Afrikanische Kooperationsprojekte in der Infektiologie (DFG-Projekt KR 1150/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.