QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 2 December 2003
doi: 10.1242/jcs.00860

This Article Figures Only Full Text Full Text (PDF) Supplemental Data All Versions of this Article: jcs.00860v1 117/2/315    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prina, E. Articles by Antoine, J.-C. Search for Related Content PubMed PubMed Citation Articles by Prina, E. Articles by 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

¹ Unité d'Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur, Paris, France ² Centre d'Imagerie Dynamique, Institut Pasteur, Paris, France and ³ Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France

^* Author for correspondence (e-mail: eprina{at}pasteur.fr)

Accepted 5 September 2003

In their mammalian hosts, Leishmania are obligate intracellular parasites that mainly reside in macrophages. They are also phagocytosed by dendritic cells (DCs), which play decisive roles in the induction and shaping of T cell-dependent immune responses. Little is known about the role of DCs in the Leishmania life cycle. Here, we examined the ability of mouse bone marrow-derived DCs to serve as hosts for L. amazonensis. Both infective stages of Leishmania (metacyclic promastigotes and amastigotes) could be phagocytosed by DCs, regardless of whether they had previously been experimentally opsonized with either the complement C3 component or specific antibodies. Parasites could survive and even multiply in these cells for at least 72 hours, within parasitophorous vacuoles displaying phagolysosomal characteristics and MHC class II and H-2M molecules. We then studied the degree of maturation reached by infected DCs according to the parasite stage internalised and the type of opsonin used. The cell surface expression of CD24, CD40, CD54, CD80, CD86, OX40L and MHC class II molecules was barely altered following infection with unopsonized promastigotes or amastigotes from nude mice or with C3-coated promastigotes. Even 69 hours post-phagocytosis, a large proportion of infected DCs remained phenotypically immature. In contrast, internalisation of antibody-opsonized promastigotes or amastigotes induced DCs to mature rapidly, as shown by the over-expression of costimulatory, adhesion and MHC class II molecules. Thus, in the absence of specific antibodies (e.g. shortly after infecting naive mammals), infected DCs may remain immature or semi-mature, meaning that they are unable to elicit an efficient anti-Leishmania T cell response. Absence of DC maturation or delayed/incomplete DC maturation could thus be beneficial for the parasites, allowing their establishment and amplification before the onset of immune responses.

Key words: Leishmania, Promastigote, Amastigote, Dendritic cell, Phagocytosis, Parasitophorous vacuole, Maturation

This article has been cited by other articles:

				D. A. Vargas-Inchaustegui, L. Xin, and L. Soong Leishmania braziliensis Infection Induces Dendritic Cell Activation, ISG15 Transcription, and the Generation of Protective Immune Responses J. Immunol., June 1, 2008; 180(11): 7537 - 7545. [Abstract] [Full Text] [PDF]

				L. Soong Modulation of Dendritic Cell Function by Leishmania Parasites J. Immunol., April 1, 2008; 180(7): 4355 - 4360. [Abstract] [Full Text] [PDF]

				C. Favali, N. Tavares, J. Clarencio, A. Barral, M. Barral-Netto, and C. Brodskyn Leishmania amazonensis infection impairs differentiation and function of human dendritic cells J. Leukoc. Biol., December 1, 2007; 82(6): 1401 - 1406. [Abstract] [Full Text] [PDF]

				L. Xin, Y. Li, and L. Soong Role of Interleukin-1{beta} in Activating the CD11chigh CD45RB Dendritic Cell Subset and Priming Leishmania amazonensis- Specific CD4+ T Cells In Vitro and In Vivo Infect. Immun., October 1, 2007; 75(10): 5018 - 5026. [Abstract] [Full Text] [PDF]

				U. Korner, V. Fuss, J. Steigerwald, and H. Moll Biogenesis of Leishmania major-Harboring Vacuoles in Murine Dendritic Cells Infect. Immun., February 1, 2006; 74(2): 1305 - 1312. [Abstract] [Full Text] [PDF]

				M. Breton, M. J Tremblay, M. Ouellette, and B. Papadopoulou Live Nonpathogenic Parasitic Vector as a Candidate Vaccine against Visceral Leishmaniasis Infect. Immun., October 1, 2005; 73(10): 6372 - 6382. [Abstract] [Full Text] [PDF]

				D. Chakraborty, S. Banerjee, A. Sen, K. K. Banerjee, P. Das, and S. Roy Leishmania donovani Affects Antigen Presentation of Macrophage by Disrupting Lipid Rafts J. Immunol., September 1, 2005; 175(5): 3214 - 3224. [Abstract] [Full Text] [PDF]

				J. Ji, J. Masterson, J. Sun, and L. Soong CD4+CD25+ Regulatory T Cells Restrain Pathogenic Responses during Leishmania amazonensis Infection J. Immunol., June 1, 2005; 174(11): 7147 - 7153. [Abstract] [Full Text] [PDF]

				R. C. Hespanhol, M. de Nazare C. Soeiro, M. B. Meuser, M. de Nazareth S.L. Meirelles, and S. Corte-Real The Expression of Mannose Receptors in Skin Fibroblast and Their Involvement in Leishmania (L.) amazonensis Invasion J. Histochem. Cytochem., January 1, 2005; 53(1): 35 - 44. [Abstract] [Full Text] [PDF]