Cutting Edge: Carbohydrate Profiling Identifies New Pathogens That Interact with Dendritic Cell-Specific ICAM-3-Grabbing Nonintegrin on Dendritic Cells

Abstract

Dendritic cells (DC) are instrumental in handling pathogens for processing and presentation to T cells, thus eliciting an appropriate immune response. C-type lectins expressed by DC function as pathogen-recognition receptors; yet their specificity for carbohydrate structures on pathogens is not fully understood. In this study, we analyzed the carbohydrate specificity of DC-specific ICAM-3-grabbing nonintegrin (SIGN)/CD209, the recently documented HIV-1 receptor on DC. Our studies show that DC-SIGN binds with high affinity to both synthetic mannose- and fucose-containing glycoconjugates. These carbohydrate structures are abundantly expressed by pathogens as demonstrated by the affinity of DC-SIGN for natural surface glycans of the human pathogens Mycobacterium tuberculosis, Helicobacter pylori, Leishmania mexicana, and Schistosoma mansoni. This analysis expands our knowledge on the carbohydrate and pathogen-specificity of DC-SIGN and identifies this lectin to be central in pathogen-DC interactions.

Specific Recognition of Leishmania major Poly-β-galactosyl Epitopes by Galectin-9

“…Using this technique, we were able to find unique oligosaccharides such as poly-␤-galactose epitope which can bind to a galectin. Recent advances in the determination of rare oligosaccharide structures and in the discovery of glycosyltransferases that synthesize those rare glycans began to reveal various unique carbohydrate structures that play crucial roles in cellular communication during nonself pathogen recognition or other cellular activities (6,(73)(74)(75). Therefore, employment of FAC analysis would broaden the horizons to find such specific lectin ligands easily in the future with limited amounts of novel oligosaccharides.…”

Carbohydrate‐Mediated Targeting of Antigen to Dendritic Cells Leads to Enhanced Presentation of Antigen to T Cells

“…In addition, carbohydrate profiling by another group has revealed that DC-SIGN can recognize non-sialylated Lewis blood group antigens (e.g., Lewis x ). [16] Five murine homologues of DC-SIGN have been described; one homologue, CIRE is expressed exclusively in CD8α − CD4 + and CD8α − CD4 − DCs, [17] and another homologue, mSIGNR1, is expressed on marginal zone macrophages and is capable of recognizing both high-mannose oligosaccharides and Lewis antigens. [18] Although recent studies have demonstrated that murine CIRE is not a functional homologue of DC-SIGN, [19] we wished to address the possibility that a lectin with a DC-SIGN-like binding profile might be mediating the recognition and uptake of (OVA)-1.…”

Multiple Modes of Binding Enhance the Affinity of DC-SIGN for High Mannose N-Linked Glycans Found on Viral Glycoproteins

“…Although the epitope for T cell interactions has not been defined, interactions with pathogens exploit the ability of DC-SIGN to recognize both branched fucosylated structures bearing terminal galactose residues and high mannose N-linked oligosaccharides (3)(4)(5). The latter specificity allows DC-SIGN to act as a receptor for several enveloped viruses that bear high mannose structures on their surface glycoproteins, most notably human immunodeficiency virus (HIV)…”