C‐type lectin receptors MR and DC‐SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells

Hemocyanins are used as immunomodulators in clinical applications because they induce a strong Th1-biased cell-mediated immunity, which has beneficial effects. They multiligand glycosylated molecules with abundant and complex mannose-rich structures. It remains unclear whether these structures influence hemocyanin-induced immunostimulatory processes human APCs. We have previously shown that hemocyanin glycans from Concholepas concholepas (CCH), Fissurella latimarginata (FLH), Megathura crenulata (KLH), participate their immune recognition immunogenicity mice, interacting murine C-type lectin receptors (CLRs). Here, we studied the interactions of hemocyanins two major mannose-binding CLRs on monocyte-derived DCs: MR (mannose receptor) DC-SIGN (DC-specific ICAM-3–grabbing nonintegrin). Diverse analyses showed internalized by mannose-sensitive mechanism. This process was calcium dependent. Moreover, colocalized DC-SIGN, were partly through clathrin-mediated endocytosis. The hemocyanin-mediated proinflammatory cytokine response impaired when using deglycosylated FLH KLH compared to CCH. further bind carbohydrate-dependent manner affinity constants physiological concentration range. Overall, three clinically valuable interact CLRs, initiating an promoting Th1 cell-driving potential.