DC-SIGN in Infection and Immunity

Abstract

Dendritic cells (DCs) play a central role in the immune system by patrolling peripheral tissues to sample antigens to induce antigen-specific adaptive immune responses in lymphoid tissues. DCs express pattern recognition receptors such as toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and C-type lectin receptors (CLRs) to interact with pathogens for antigen presentation and immune activation. One of the CLRs involved in different processes of DC function is DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). DC-SIGN recognition of pathogens leads to efficient internalization and processing of antigen for MHC class I and II presentation. In addition, triggering of DC-SIGN induces intracellular signaling that affects immune responses. Although DC-SIGN signaling by itself does not lead to activation of transcription factors such as NFκB, it greatly modifies signaling pathways induced by other receptors, including TLRs, RLRs, and interferon receptors. Modulation of signaling pathways by DC-SIGN tailors adaptive immune responses to different pathogens by driving specific T-helper cell responses. Intriguingly, DC-SIGN signaling depends on the carbohydrate structures present on pathogens as mannose structures induce very different signaling cascades than fucose structures, providing DCs with the plasticity to tailor immune responses to a diverse range of pathogens. Several pathogens however have evolved to subvert DC-SIGN functions for effective infection of DCs and efficient transmission to target cells. In this chapter we will discuss DC-SIGN structure, expression, and DC-SIGN functionality in shaping adaptive immune responses and immunopathogenesis.