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Originally published In Press as doi:10.1074/jbc.M205270200 on July 16, 2002

J. Biol. Chem., Vol. 277, Issue 39, 36766-36769, September 27, 2002
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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 Leishmania Amastigotes*

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

From the Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Velázquez 144, 28006 Madrid, Spain

Dendritic cells (DCs) play a critical role in the initiation of the immunological response against Leishmania parasites. However, the receptors involved in amastigote-dendritic cell 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 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. pifanoi amastigotes interact with immature human dendritic cells and CD209-transfected K562 cells in a time- and dose-dependent manner. Leishmania amastigote 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 Leishmania amastigotes 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 Leishmania amastigote uptake by dendritic cells. Our finding has important implications for Leishmania host-cell interaction and the immunoregulation of cutaneous leishmaniasis.

* This work was supported in part by Grants SAF98/0068 (Comisión Interministerial de Ciencia y Tecnología), 08.3/0026/2000.1 (Comunidad de Madrid), and 01/0063-01 (Fondo de Investigaciones Sanitarias) (to A. L. C.) and Programa General de Grupos Estratégicos (Comunidad Autónoma de Madrid), Grant 99/0025-02 (Fondo de Investigaciones Sanitarias), and Grant QLRT-2000-01404 (European Union) (to L. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by a postdoctoral fellowship (Comunidad de Madrid).

§ Supported by a grant from the Fundación Renal Iñigo Alvarez de Toledo.

To whom correspondence should be addressed. Tel.: 34-915-611-800, ext. 4312; Fax: 34-915-627-518; E-mail: acorbi@cib.csic.es.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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