title: Human intestinal epithelial cells respond to β-glucans via Dectin-1 and Syk.
abstract: Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and may be involved in intestinal immune responses. Fungi are important components of the intestinal microflora. The potential role of fungi, and in particular their cell wall component β-glucan, in modulating human intestinal epithelial responses is still unclear. Here we examined whether human IECs are capable of recognizing and responding to β-glucans, and the potential mechanisms of their activation. We show that human IECs freshly isolated from surgical specimens, and the human IEC lines HT-29 and SW480, express the β-glucan receptor Dectin-1. The β-glucan-consisting glycans curdlan and zymosan stimulated IL-8 and CCL2 secretion by IEC lines. This was significantly inhibited by a Dectin-1 blockade using its soluble antagonist laminarin. Spleen tyrosine kinase (Syk), a signaling mediator of Dectin-1 activation, is expressed in human IECs. β-glucans and Candida albicans induced Syk phosphorylation, and Syk inhibition significantly decreased β-glucan-induced chemokine secretion from IECs. Thus, IECs may respond to β-glucans by the secretion of pro-inflammatory chemokines in a Dectin-1- and Syk-dependent pathway, via receptors and a signaling pathway described to date only for myeloid cells. These findings highlight the importance of fungi-IEC interactions in intestinal inflammation.
authors.affiliation: Inflammatory Bowel Diseases Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Cohen-Kedar
authors.forename: Liran
authors.initials: L
authors.lastname: Baram
authors.forename: Hofit
authors.initials: H
authors.lastname: Elad
authors.forename: Eli
authors.initials: E
authors.lastname: Brazowski
authors.forename: Hanan
authors.initials: H
authors.lastname: Guzner-Gur
authors.forename: Iris
authors.initials: I
authors.lastname: Dotan
mesh_terms: D002460:Cell Line; D018932:Chemokine CCL2 / Q000276:immunology*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D000072377:Syk Kinase; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D018932:Chemokine CCL2; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D047071:beta-Glucans; C111835:CCL2 protein, human; C546929:CLEC7A protein, human; D000099181:Dectin-1; C508606:CXCL8 protein, human; C000606896:SYK protein, human
keywords: Dectin-1 ⋅ Epithelial cells ⋅ Inflammation ⋅ Intestinal immunity ⋅ Mucosal immunity