Dendritic Cell (DC)-specific Intercellular Adhesion Molecule 3 (ICAM-3)-grabbing Nonintegrin (DC-SIGN, CD209), a C-type Surface Lectin in Human DCs, Is a Receptor for LeishmaniaAmastigotes*

Dendritic cells (DCs) play a critical role in the initiation of the immunological response against Leishmaniaparasites. However, the receptors involved in amastigote-dendritic cell interaction are unknown, especially in absence of opsonizing antibodies. We have studied the interaction of Leishmania pifanoiaxenic amastigotes with the C-type lectin DC-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN, CD209), a receptor for ICAM-2, ICAM-3, human immunodeficiency virus gp120, and Ebola virus. L. pifanoiamastigotes interact with immature human dendritic cells and CD209-transfected K562 cells in a time- and dose-dependent manner. Leishmaniaamastigote binding to human dendritic cells and DC-SIGN-transfected cells is inhibited by a function-blocking DC-SIGN-specific monoclonal antibody. More importantly, this monoclonal antibody dramatically reduces internalization of Leishmaniaamastigotes by immature human DCs. These results constitute the first description of a nonviral pathogen ligand for DC-SIGN and provide evidence for a relevant role of DC-SIGN in Leishmaniaamastigote uptake by dendritic cells. Our finding has important implications forLeishmaniahost-cell interaction and the immunoregulation of cutaneous leishmaniasis.