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