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Staphylococcus aureus convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) T cells via the

Hardis Rabe1, Inger Nordström, Kerstin Andersson

  • 1Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Immunology
|April 9, 2014
PubMed

Insights

Newborns have fewer regulatory T (Treg) cells, but Staphylococcus aureus can induce these crucial immune cells in infants. This bacterial induction of Treg cells in newborns occurs via the PD-1/PD-L1 pathway.

Area of Science:

  • Immunology
  • Microbiology
  • Neonatal Health

Background:

  • The gut microbiota's role in inducing regulatory T (Treg) cells is established in mice but unknown in newborns.
  • Staphylococcus aureus is a common gut colonizer in Swedish infants, prompting investigation into its immunological effects.

Purpose of the Study:

  • To investigate the in vitro effects of bacterial stimulation on neonatal CD4(+) T cells for inducing CD25(+) CD127(low) Treg cells.
  • To compare Treg cell populations and their markers (FOXP3, Helios, CTLA-4) in newborns and adults.
  • To determine if Staphylococcus aureus can induce Treg cells in neonatal and adult immune cells.

Main Methods:

  • Co-culture of non-Treg cells with Treg cells and mononuclear cells, stimulated with S. aureus.
  • Flow cytometry analysis of CD25(+) CD127(low) Treg cells and expression of FOXP3, Helios, and CTLA-4.
  • Use of CellTrace violet staining and sorted naive CD45RA(+) cells for specific cell population analysis.
  • Assessment of Treg cell suppressive function and the role of the PD-1/PD-L1 axis via PD-L1 blocking.

Main Results:

  • Newborns had fewer circulating CD25(+) CD127(low) Treg cells than adults, but these cells showed higher Helios(+) and CTLA-4(+) expression.
  • S. aureus stimulation induced FOXP3(+) CD25(+) CD127(low) T cells primarily in neonatal non-Treg cells.
  • S. aureus induced fewer FOXP3(+) cells in adult non-Treg cells compared to newborns, unless naive cells were used.
  • Neonatal Treg cells from S. aureus-stimulated cultures retained suppressive function.
  • Blocking PD-L1 significantly reduced the induction of FOXP3(+) CD25(+) CD127(low) T cells.

Conclusions:

  • Newborns possess a higher proportion of thymically derived Helios(+) Treg cells compared to adults.
  • Staphylococcus aureus can convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) Treg cells.
  • This conversion is mediated through the PD-1/PD-L1 pathway, highlighting a specific neonatal immune response to bacterial colonization.

Keywords:
FOXP3+ regulatory T cellsHeliosStaphylococcus aureuscord bloodprogrammed cell death 1

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