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Papers In Press, published online ahead of print July 16, 2002
J. Biol. Chem, 10.1074/jbc.M205270200
Submitted on May 29, 2002
Revised on July 10, 2002
Accepted on July 15, 2002

Dendritic-cell specific ICAM-3 grabbing nonintegrin (DC-SIGN, CD209), a C-type surface lectin in human dendritic cells, is a receptor for Leishmania amastigotes

María Colmenares, Amaya Puig-Kröger, Oscar Muñiz Pello, Angel L. Corbí, and Luis Rivas

Department of Immunology, Consejo Superior de Investigaciones Científicas, Madrid, Madrid 28006

Corresponding Author: acorbi{at}cib.csic.es

Dendritic cells (DC) play a critical role in the initiation of the immunological response against Leishmania parasites. However, the receptors involved in amastigote-dendritic cells interaction are unknown, especially in absence of opsonizing antibodies. We have studied the interaction of Leishmania pifanoi axenic amastigotes with the C-type lectin DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN, CD209), a receptor for ICAM-2, ICAM-3, HIV gp120 and Ebola virus. L. pifanoi amastigotes interact with immature human dendritic cells and CD209 transfected K562 cells in a time-and dose dependent manner. Leishmania amastigotes 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 reduces dramatically internalization of Leishmania amastigotes by immature human DC´s. These results constitute the first description of a non-viral pathogen ligand for DC-SIGN and provide evidence for a relevant role of DC-SIGN in Leishmania amastigote uptake by dendritic cells. Our finding has important implications for Leishmania host-cell interaction and the immunoregulation of cutaneous leishmaniasis.


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