Human DC-SIGN binds specific human milk glycans

• Published in: Biochemical journal Vol. 473; no. 10; p. 1343
• Main Authors: Noll, Alexander J, Yu, Ying, Lasanajak, Yi, Duska-McEwen, Geralyn, Buck, Rachael H, Smith, David F, Cummings, Richard D
• Format: Journal Article
• Language: English
• Published: England 15.05.2016
• Subjects: Cell Adhesion Molecules - metabolism; Dendritic Cells - metabolism; Humans; Lectins, C-Type - metabolism; Milk, Human - chemistry; Polysaccharides - metabolism; Protein Array Analysis; Protein Binding; Receptors, Cell Surface - metabolism; Sialic Acid Binding Immunoglobulin-like Lectins - metabolism; Trisaccharides - metabolism; glycan recognition; glycan-binding proteins; dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN); human milk glycans; glycan microarrays; lectins
• ISSN: 1470-8728
• DOI: 10.1042/BCJ20160046

Human milk glycans (HMGs) are prebiotics, pathogen receptor decoys and regulators of host physiology and immune responses. Mechanistically, human lectins (glycan-binding proteins, hGBP) expressed by dendritic cells (DCs) are of major interest, as these cells directly contact HMGs. To explore such interactions, we screened many C-type lectins and sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed by DCs for glycan binding on microarrays presenting over 200 HMGs. Unexpectedly, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) showed robust binding to many HMGs, whereas other C-type lectins failed to bind, and Siglec-5 and Siglec-9 showed weak binding to a few glycans. By contrast, most hGBP 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'-fucosyl-lactose (2'-FL) and 3-fucosyl-lactose (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 hGBP expressed by DCs binds to α-fucosylated HMGs, and suggest that such interactions may be important in influencing immune responses in the developing infant.