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

Autor: Veronica Ayechu-Muruzabal, Saskia A. Overbeek, Atanaska I. Kostadinova, Bernd Stahl, Johan Garssen, Belinda van’t Land, Linette E.M. Willemsen
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Biomolecules, Vol 10, Iss 5, p 784 (2020)
Druh dokumentu: article
ISSN: 2218-273X
DOI: 10.3390/biom10050784
Popis: 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.
Databáze: Directory of Open Access Journals
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