The oligosaccharides 6'-sialyllactose, 2'-fucosyllactose or galactooligosaccharides do not directly modulate human dendritic cell differentiation or maturation

PLoS One. 2018 Jul 10;13(7):e0200356. doi: 10.1371/journal.pone.0200356. eCollection 2018.

Abstract

Breast milk plays an important role in immune development in early life and protects against diseases later in life. A wide range of the beneficial effects of breast milk are attributed to human milk oligosaccharides (HMOs) as well as components such as vitamin D3 (VitD3) or TGFβ. One mechanism by which HMOs might contribute to immune homeostasis and protection against disease is the induction of a local tolerogenic milieu. In this study we investigated the effect of the HMOs 6'-sialyllactose (6'SL) and 2'-fucosyllactose (2'FL) as well as prebiotic galactooligosaccharides (GOS) on DC differentiation and maturation. Isolated CD14+ monocytes were cultured for six days in the presence of GM-CSF and IL-4 with or without 6'SL, 2'FL, GOS, VitD3 or TGFβ. Additionally, immature VitD3DC, TGFβDC and moDC were used as different DC types to investigate the effect of 6'SL, 2'FL and GOS on DC maturation. Surface marker expression and cytokine production was measured by flow cytometry and cytometric bead array, respectively. Unlike TGFβ and vitD3, the oligosaccharides 6'SL, 2'FL and GOS did not influence DC differentiation. Next, we studied the effect of 6'SL, 2'FL and GOS on maturation of moDC, VitD3DC and TGFβDC that showed different profiles of HMO-binding receptors. 6'SL, 2'FL and GOS did not modulate LPS-induced maturation, even though their putative receptors were present on the different DCs types. Thus, whereas VitD3 and TGFβ halt DC differentiation, which results in phenotypically distinct tolerogenic DCs, 6'SL, 2'FL and GOS do not alter DC differentiation or maturation of in vitro differentiated DC types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / metabolism
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cerebrospinal Fluid / metabolism
  • Dendritic Cells / metabolism*
  • Humans
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / metabolism
  • Lactose / administration & dosage
  • Lactose / analogs & derivatives*
  • Lactose / metabolism
  • Milk, Human / metabolism
  • Oligosaccharides / administration & dosage
  • Oligosaccharides / metabolism*
  • Prebiotics
  • Transforming Growth Factor beta / metabolism
  • Trisaccharides / administration & dosage
  • Trisaccharides / metabolism*

Substances

  • 6'-sialyllactose
  • IL4 protein, human
  • Oligosaccharides
  • Prebiotics
  • Transforming Growth Factor beta
  • Trisaccharides
  • Interleukin-4
  • Calcitriol
  • Lactose
  • 2'-fucosyllactose

Grants and funding

This work was supported by the Netherlands Organisation of Scientific Research (NWO) as part of the technology foundation STW (project number 13017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Friesland Campina provided support in the form of salary for author RJJvN, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.