Exposure of Intestinal Epithelial Cells to 2'-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-05, Vol.10 (5), p.784
• Main Authors: Ayechu-Muruzabal, Veronica, Overbeek, Saskia A, Kostadinova, Atanaska I, Stahl, Bernd, Garssen, Johan, Van't Land, Belinda, Willemsen, Linette E M
• Format: Article
• Language: English
• Subjects: 2′-fucosyllactose 2; Blood; Breast milk; CD28 antigen; CD4 antigen; Cell culture; Cells, Cultured; Coculture Techniques - methods; CpG islands; Culture Media, Conditioned - pharmacology; Cytokines; Dendrites; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; dendritic cells 6; Deoxyribonucleic acid; DNA; Enterocytes - drug effects; Enterocytes - metabolism; Epithelial cells; Flow cytometry; Galectin-3; Galectin-9; Galectins - metabolism; galectins 4; Homeostasis; HT29 Cells; Humans; Immunomodulation; Interferon-gamma - metabolism; Interleukin 10; Interleukin 13; Interleukin-10 - metabolism; intestinal epithelial cells 5; Intestine; Intestines; Lactose; Lectins; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation; Lymphocytes T; Milk; Mimicry; Monocytes; Mucosal immunity; non-digestible oligosaccharides 3; Oligodeoxyribonucleotides - pharmacology; Oligosaccharides; Peripheral blood mononuclear cells; Physiological aspects; Th1 Cells - drug effects; Th1 Cells - immunology; Transforming Growth Factor beta - metabolism; Transforming growth factor-b1; Trisaccharides - pharmacology; γ-Interferon
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10050784

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.