Human milk oligosaccharides promote immune tolerance via direct interactions with human dendritic cells

Ling Xiao, Wouter Rph van De Worp, Roderick Stassen, Celine van Maastrigt, Nienke Kettelarij, Bernd Stahl, Bernadet Blijenberg, Saskia A. Overbeek, Gert Folkerts, Johan Garssen, Belinda Van't Land*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Web of Science)

Abstract

Human milk oligosaccharides (HMOS) are a complex mixture of bioactive components supporting the immune development of breastfed-infants. Dendritic cells (DCs) play a central role in the regulation of immune responses, being specialized in antigen presentation and driving T-cell priming as well as differentiation. However, little is known about the direct effects of HMOS on human DC phenotypes and functions. Here, we report that HMOS mixture isolated from pooled human milk, induced semi-maturation of human monocytes-derived DCs (moDCs), and elevated levels of IL-10, IL-27 and IL-6 but not IL-12p70 and TNF-alpha. Consistently, HMOS-conditioned human moDCs promoted Treg generation from naive CD4(+) T cells. Interestingly, HMOS limited LPS-induced maturation of human moDCs, while maintained IL-10 and IL-27 secretion and reduced LPS-induced production of IL-12p70, IL-6 and TNF-alpha. Furthermore, HMOS+LPS-stimulated DCs induced a higher frequency of Tregs and increased IL-10 production, while a reduction in Tbet+Th1 frequency and IFN-gamma production was detected as compared to LPS-DCs. The regulatory effects of HMOS seemed to be mediated by interactions of HMOS with receptors, including but not limited to TLR4 and DC-SIGN on human moDCs. In conclusion, HMOS contain tolerogenic factors influencing human moDCs and thereby modulating the development of the neonatal immune system.

Original languageEnglish
Pages (from-to)1001-1014
Number of pages14
JournalEuropean Journal of Immunology
Volume49
Issue number7
DOIs
Publication statusPublished - Jul 2019

Keywords

  • DC-SIGN
  • human milk oligosaccharides
  • IL-10
  • regulatory T cells (Treg)
  • TLR4
  • BREAST-MILK
  • T-CELLS
  • ACTIVATION
  • PHENOTYPE
  • INNATE

Cite this