In their mammalian hosts, Leishmania are obligate intracellular parasites that reside in macrophages and dendritic cells (DCs). In the present study, we have investigated in vitro the mechanisms of entry into human DCs of Leishmania amazonensis amastigotes isolated from lesions in nude mice (Am nude). The DC infection rate with Am nude was approximately 36%, while opsonization of Am nude with normal human serum and infected human serum increased the DC infection rates to 60% and 62%, respectively. Heat inactivation and depletion of antibodies in sera brought the DC infection rate down to 40%. The DC infection rate was inhibited after pre-treatment of Am nude with heparin. We were unable to implicate mannose-fucose receptors in the uptake of Am nude by DCs. Our data suggest that the ability of L. amazonensis amastigotes to infect human DCs involves the participation of at least three multiple receptor-ligand interactions, antibodies/FcR, complement components/CR and proteoglycans/heparin-binding protein. © 2007 Elsevier Inc. All rights reserved.1163306310Arrais-Silva, W.W., Colhone, M.C., Ayres, D.C., Souto, P.C.S., Giorgio, S., Effects of hyperbaric oxygen on Leishmania amazonensis promastigotes and amastigotes (2005) Parasitology International, 54, pp. 1-7Avila, J.L., Rojas, M., Galili, U., Immunogenic Gal alpha 1-3Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania (1989) The Journal of Immunology, 142, pp. 2828-2834Barbieri, C.L., Giorgio, S., Merjan, A.J., Figueiredo, E.N., Glycosphingolipid antigens of Leishmania (Leishmania) amazonensis amastigotes identified by use of a monoclonal antibody (1993) Infection and Immunity, 61, pp. 2131-2137Blackwell, J.M., Ezekowitz, R.A., Roberts, M.B., Channon, J.Y., Sim, R.B., Gordon, S., Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum (1985) The Journal of Experimental Medicine, 162, pp. 324-331Blank, C., Fuchs, H., Rappersberger, K., Rollinghoff, M., Moll, H., Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major (1993) The Journal of Infectious Diseases, 167, pp. 418-425Brandonisio, O., Spinelli, R., Pepe, M., Dendritic cells in Leishmania infection (2004) Microbes and Infection, 6, pp. 1402-1409Butcher, B.A., Sklar, L.A., Seamer, L.C., Glew, R.H., Heparin enhances the interaction of infective Leishmania donovani promastigotes with mouse peritoneal macrophages. A fluorescence flow cytometric analysis (1992) The Journal of Immunology, 148, pp. 2879-2886Cantos, G., Barbieri, C.L., Iacomini, M., Gorin, P.A., Travassos, L.R., Synthesis of antimony complexes of yeast mannan and mannan derivatives and their effect on Leishmania-infected macrophages (1993) The Biochemical Journal, 289, pp. 155-160Chakraborty, P., Ghosh, D., Basu, M.K., Modulation of macrophage mannose receptor affects the uptake of virulent and avirulent Leishmania donovani promastigotes (2001) The Journal of Parasitology, 87, pp. 1023-1027Colmenares, M., Corbi, A.L., Turco, S.J., Rivas, L., The dendritic cell receptor DC-SIGN discriminates among species and life cycle forms of Leishmania (2004) The Journal of Immunology, 172, pp. 1186-1190Colmenares, M., Puig-Kroger, A., Pello, O.M., Corbi, A.L., Rivas, L., 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 (2002) The Journal of Biological Chemistry, 277, pp. 36766-36769Dominguez, M., Torano, A., Immune adherence-mediated opsonophagocytosis: the mechanism of Leishmania infection (1999) The Journal of Experimental Medicine, 189, pp. 25-35Grimaldi, G.R., Tesh, R.B., Leishmaniases of the New World: current concepts and implications for future research (1993) Clinical Microbiology Reviews, 6, pp. 230-250Guy, R.A., Belosevic, M., Comparison of receptors required for entry of Leishmania major amastigotes into macrophages (1993) Infection and Immunity, 61, pp. 1553-1558Handman, E., Cell biology of Leishmania (1999) Advances in Parasitology, 44, pp. 1-39Kima, P.E., Constant, S.L., Hannum, L., Colmenares, M., Lee, K.S., Haberman, A.M., Shlomchik, M.J., McMahon-Pratt, D., Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis (2000) The Journal of Experimental Medicine, 191, pp. 1063-1067Kolb-Maurer, A., Pilgrim, S., Kampgen, E., McLellan, A.D., Brocker, E.B., Goebel, W., Gentschev, I., Antibodies against listerial protein 60 act as an opsonin for phagocytosis of Listeria monocytogenes by human dendritic cells (2001) Infection and Immunity, 69, pp. 3100-3109Laufs, H., Muller, K., Fleischer, J., Reiling, N., Jahnke, N., Jensenius, J.C., Solbach, W., Laskay, T., Intracellular survival of Leishmania major in neutrophil granulocytes after uptake in the absence of heat-labile serum factors (2002) Infection and Immunity, 70, pp. 826-835Love, D.C., Esko, J.D., Mosser, D.M., A heparin-binding activity on Leishmania amastigotes which mediates adhesion to cellular proteoglycans (1993) The Journal of Cell Biology, 123, pp. 759-766Mosser, D.M., Edelson, P.J., The mouse macrophage receptor for C3bi (CR3) is a major mechanism in the phagocytosis of Leishmania promastigotes (1985) The Journal of Immunology, 135, pp. 2785-2789Nair, S.K., Boczkowski, D., Morse, M., Cumming, R.I., Lyerly, H.K., Gilboa, E., Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA (1998) Nature Biotechnology, 16, pp. 364-369Navin, T.R., Krug, E.C., Pearson, R.D., Effect of immunoglobulin M from normal human serum on Leishmania donovani promastigote agglutination, complement-mediated killing, and phagocytosis by human monocytes (1989) Infection and Immunity, 57, pp. 1343-1346Peters, C., Aebischer, T., Stierhof, Y.D., Fuchs, M., Overath, P., The role of macrophage receptors in adhesion and uptake of Leishmania mexicana amastigotes (1995) Journal of Cell Science, 108, pp. 3715-3724Prina, E., Abdi, S.Z., Lebastard, M., Perret, E., Winter, N., Antoine, J.C., Dendritic cells as host cells for the promastigote and amastigote stages of Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic cell maturation (2004) Journal of Cell Science, 117, pp. 315-325Wilson, M.E., Pearson, R.D., Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism (1986) The Journal of Immunology, 136, pp. 4681-4688Woelbing, F., Kostka, S.L., Moelle, K., Belkaid, Y., Sunderkoetter, C., Verbeek, S., Waisman, A., von Stebut, E., Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors and facilitates acquisition of protective immunity (2006) The Journal of Experimental Medicine, 203, pp. 177-188