Dendritic cells: a spot on sialic Acid

Abstract

Glycans decorating cell surface and secreted proteins and lipids occupy the juncture where critical host-host and host-pathogen interactions occur. The role of glycan epitopes in cell-cell and cell-pathogen adhesive events is already well-established, and cell surface glycan structures change rapidly in response to stimulus and inflammatory cues. Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how glycans and their changes contribute to the overall immune response remains poorly defined. Sialic acids are unique sugars that usually occupy the terminal position of the glycan chains and may be modified by external factors, such as pathogens, or upon specific physiological cellular events. At cell surface, sialic acid-modified structures form the key fundamental determinants for a number of receptors with known involvement in cellular adhesiveness and cell trafficking, such as the Selectins and the Siglec families of carbohydrate recognizing receptors. Dendritic cells (DCs) preside over the transition from innate to the adaptive immune repertoires, and no other cell has such relevant role in antigen screening, uptake, and its presentation to lymphocytes, ultimately triggering the adaptive immune response. Interestingly, sialic acid-modified structures are involved in all DC functions, such as antigen uptake, DC migration, and capacity to prime T cell responses. Sialic acid content changes along DC differentiation and activation and, while, not yet fully understood, these changes have important implications in DC functions. This review focuses on the developmental regulation of DC surface sialic acids and how manipulation of DC surface sialic acids can affect immune-critical DC functions by altering antigen endocytosis, pathogen and tumor cell recognition, cell recruitment, and capacity for T cell priming. The existing evidence points to a potential of DC surface sialylation as a therapeutic target to improve and diversify DC-based therapies.

Keywords: dendritic cell; host-pathogen interaction; lectins; sialic acid; sialylation.

Figure 1

Dendritic cell (DC) immune functions. DCs act on three main events: the antigen capture after interaction with host cells, microbial agents, and tumor cells by recognizing Pathogen-Associated Molecular Patterns (PAMPs) and self molecules through Pathogen Recognition Receptors (PRRs) and other cell surface receptors like Siglecs or C-type Lectins (CLRs); maturation and migration toward the secondary lymphoid organs; T cell activation where DCs present the processed antigens to T cells eliciting a specific and enduring response or tolerance from T cells.

Figure 2

General overview of the dendritic cell functions modulated by sialylation. Sialic acid-containing glycans actively participate and modulate processes like: cell adhesion during migration and homing; or in “de facto” immune processes such as tumor cell recognition and microbial recognition, overall modulating the immune response/tolerance balance.