Abstract
Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2′-fucosyllactose (2′-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using a co-culture model developed to study the crosstalk between IEC and innate and adaptive immune cells. IECs, co-cultured with αCD3/CD28-activated peripheral blood mononuclear cells (PBMC), were apically exposed to NDOs and CpG, washed and co-cultured with immature monocyte-derived dendritic cells (moDC). Subsequently, moDC were co-cultured with naïve CD4+ T-cells. In the presence of CpG, both 2′-FL or GF-exposed IEC enhanced Th1-type IFNγ and regulatory IL-10 secretion of PBMCs, compared to CpG alone, while Th2-type IL-13 was reduced. Both NDOs increased IEC-derived galectin-3, -4, -9 and TGF-β1 of CpG-exposed IEC. Only galectin-9 correlated with all modified immune parameters and TGF-β1 secretion. MoDCs exposed to 2′-FL and CpG-conditioned IEC instructed IFNγ and IL-10 secretion by CD4+ T-cells, suggesting the development of a regulatory Th1 response. These results reveal that 2′-FL and GF could contribute to the mucosal immune development by supporting the effect of microbial CpG DNA associated with the modulation of epithelial galectin and TGF-β1 secretion.
Highlights
Non-digestible oligosaccharides (NDO) are abundantly present in human milk and consist of complex and diverse structures which vary during the course of lactation [1]
galacto- and long-chain fructo-oligosaccharides (GF)-exposed intestinal epithelial cells (IEC) did not give rise to this effector Th-cell response. These results indicate the ability of 2 -fucosyllactose (2 -FL) and CpG-exposed IEC to instruct monocyte-derived dendritic cells (moDC) to drive the development of naïve T-cells into Th1 and regulatory-type effector cells
This study reveals that both 2 -FL and GF can promote immunomodulatory effects under inflammatory conditions upon combined exposure with bacterial CpG DNA through the modulation of IEC function
Summary
Non-digestible oligosaccharides (NDO) are abundantly present in human milk and consist of complex and diverse structures which vary during the course of lactation [1]. Galectins are immunomodulatory glycan binding proteins highly expressed and secreted by epithelial cells [16,19] and thought to play a key role in infant immunity due to their ability to bind NDOs present in human milk [3]. TGF-β is known for its contribution in sustaining immune homeostasis and mucosal protection [20,21], and can act in conjunction with galectins [22,23,24,25]. Epithelial release of these mediators may affect both innate and adaptive mucosal immune functions. Using dietary interventions to target IEC might be of interest to instruct immune development in the gastrointestinal tract
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