Regulated recruitment of DC‐SIGN to cell–cell contact regions during zymosan‐induced human dendritic cell aggregation

Zymosan is a β‐glucan, mannan‐rich yeast particle widely used to activate the inflammatory response of immune cells. We studied the zymosan‐binding potential of human dendritic cells (hDCs) by using specific carbohydrate inhibitors and blocking monoclonal antibodies. We show that DC‐specific intercellular adhesion molecule‐grabbing nonintegrin (DC‐SIGN) is a major nonopsonic recognition receptor for zymosan on hDCs. Indeed, blocking of DC‐SIGN inhibited the inflammatory response of DCs to zymosan. We compared the zymosan‐binding capacity of hDC‐SIGN to that of Dectin‐1 and complement receptor 3 (CR3), which are receptors involved in the nonopsonic recognition of these yeast‐derived particles. Dectin‐1‐ and DC‐SIGN‐K562 cells bound to zymosan particles, whereas CR3‐K562 cells did not. DC‐SIGN and Dectin‐1 were also expressed in COS cells to compare their ability to trigger particle internalization in a nonphagocytic cell line. DC‐SIGN transfectants were unable to internalize bound particles, indicating that DC‐SIGN is primarily involved in recognition but not in particle internalization. Zymosan induced a rapid DC aggregation that was accompanied by a dramatic change of DC‐SIGN distribution in the plasma membrane. Under resting conditions, DC‐SIGN was diffusely distributed through the cell surface, displaying clusters at the free leading edge. Upon zymosan treatment, DC‐SIGN was markedly redistributed to cell–cell contacts, supporting an adhesion role in DC–DC interactions. The mechanism(s) supporting DC‐SIGN‐mediated intercellular adhesion were further investigated by using DC‐SIGN‐K562 aggregation. DC‐SIGN was highly concentrated at points of cell–cell contact, suggesting a role for enhanced avidity during DC‐SIGN‐mediated intercellular adhesion.