PMID- 12122001 OWN - NLM STAT- MEDLINE DCOM- 20021113 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 39 DP - 2002 Sep 27 TI - 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. PG - 36766-9 AB - 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. FAU - Colmenares, Maria AU - Colmenares M AD - Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Velazquez 144, 28006 Madrid, Spain. FAU - Puig-Kroger, Amaya AU - Puig-Kroger A FAU - Pello, Oscar Muniz AU - Pello OM FAU - Corbi, Angel L AU - Corbi AL FAU - Rivas, Luis AU - Rivas L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020716 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation) RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (HIV Envelope Protein gp120) RN - 0 (ICAM3 protein, human) RN - 0 (Lectins) RN - 0 (Lectins, C-Type) RN - 0 (Protozoan Proteins) RN - 0 (Receptors, Cell Surface) SB - IM MH - Animals MH - Antibodies, Monoclonal/metabolism MH - Antigens, CD/metabolism/*physiology MH - Antigens, Differentiation/metabolism/*physiology MH - Cell Adhesion Molecules/*metabolism MH - Dendritic Cells/metabolism/parasitology MH - Dose-Response Relationship, Drug MH - Ebolavirus/metabolism MH - Flow Cytometry MH - HIV Envelope Protein gp120/*metabolism MH - Humans MH - K562 Cells/*parasitology MH - Lectins/*metabolism MH - Lectins, C-Type/*metabolism MH - Leishmania/*metabolism MH - Protein Binding MH - Protozoan Proteins/*metabolism MH - Receptors, Cell Surface/*metabolism MH - Time Factors EDAT- 2002/07/18 10:00 MHDA- 2002/11/26 04:00 CRDT- 2002/07/18 10:00 PHST- 2002/07/18 10:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/07/18 10:00 [entrez] AID - S0021-9258(18)36658-4 [pii] AID - 10.1074/jbc.M205270200 [doi] PST - ppublish SO - J Biol Chem. 2002 Sep 27;277(39):36766-9. doi: 10.1074/jbc.M205270200. Epub 2002 Jul 16.