Human DC-SIGN binds specific human milk glycans

• Type of Material: Article
• Authors: Alexander J. Noll, Emory University; Ying Yu, Emory University; Yi Lasanajak, Emory University; Geralyn Duska-McEwen, Global Discovery R&D; Rachael H. Buck, Global Discovery R&D; David Smith, Emory University; Richard Cummings, Emory University
• Language: English
• Date: 2016-05-15
• Publisher: Portland Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1042/BCJ20160046
• Title of Journal or Parent Work: Biochemical Journal
• ISSN: 0264-6021
• Volume: 473
• Issue: 10
• Start Page: 1343
• End Page: 1353
• Grant/Funding Information: This work was support by NIH Grants P41GM103694 to RDC and a Grant from Abbott Nutrition, Columbus, OH.
• Keywords: RECEPTORS; dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN); human milk glycans; Biochemistry & Molecular Biology; LEWIS; glycan-binding proteins; SELECTIN; glycan recognition; glycan microarrays; lectins; EXPRESSION
• Research Categories: Biology, Molecular; Chemistry, Biochemistry

Abstract

Human milk glycans (HMGs) are prebiotics, pathogen receptor decoys, and regulators of host physiology and immune responses. Mechanistically, human lectins (glycan-binding proteins, hGBPs) expressed by dendritic cells (DC) are of major interest, as these cells directly contact HMGs. To explore such interactions, we screened many C-type lectins and Siglecs expressed by DC for glycan binding on microarrays presenting over 200 HMGs. Unexpectedly, DC-SIGN showed robust binding to many HMGs, whereas other C-type lectins failed to bind, and Siglecs-5 and -9 showed weak binding to a few glycans. By contrast, most hGBPs bound to multiple glycans on other microarrays lacking HMGs. An α-linked fucose residue was characteristic of HMGs bound by DC-SIGN. Binding of DC-SIGN to the simple HMGs 2′-fucosyllactose (2′-FL) and 3-fucosyllactose (3-FL) was confirmed by flow cytometry to beads conjugated with 2′-FL or 3-FL, as well as the ability of the free glycans to inhibit DC-SIGN binding. 2′-FL had an IC50 of ~1 mM for DC-SIGN, which is within the physiological concentration of 2′-FL in human milk. These results demonstrate that DC-SIGN among the many hGBPs expressed by DC binds to α-fucosylated HMGs, and suggest that such interactions may be important in influencing immune responses in the developing infant.