Skip to main content
Article thumbnail
Location of Repository

Uptake of Leishmania major Amastigotes Results in Activation and Interleukin 12 Release from Murine Skin–derived Dendritic Cells: Implications for the Initiation of Anti-Leishmania Immunity

By Esther von Stebut, Yasmine Belkaid, Thilo Jakob, David L. Sacks and Mark C. Udey


Epidermal Langerhans cells (LC) are immature dendritic cells (DC) located in close proximity to the site of inoculation of infectious Leishmania major metacyclic promastigotes by sand flies. Using LC-like DC expanded from C57BL/6 fetal skin, we characterized interactions involving several developmental stages of Leishmania and DC. We confirmed that L. major amastigotes, but not promastigotes, efficiently entered LC-like DC. Parasite internalization was associated with activation manifested by upregulation of major histocompatibility complex (MHC) class I and II surface antigens, increased expression of costimulatory molecules (CD40, CD54, CD80, and CD86), and interleukin (IL)-12 p40 release within 18 h. L. major–induced IL-12 p70 release by DC required interferon γ and prolonged (72 h) incubation. In contrast, infection of inflammatory macrophages (Mφ) with amastigotes or promastigotes did not lead to significant changes in surface antigen expression or cytokine production. These results suggest that skin Mφ and DC are infected sequentially in cutaneous leishmaniasis and that they play distinct roles in the inflammatory and immune response initiated by L. major. Mφ capture organisms near the site of inoculation early in the course of infection after establishment of cellular immunity, and kill amastigotes but probably do not actively participate in T cell priming. In contrast, skin DC are induced to express increased amounts of MHC antigens and costimulatory molecules and to release cytokines (including IL-12 p70) by exposure to L. major amastigotes that ultimately accumulate in lesional tissue, and thus very likely initiate protective T helper cell type 1 immunity

Topics: Brief Definitive Reports
Publisher: The Rockefeller University Press
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (1998). Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides. A role for dendritic cells in the augmentation of Th1 responses by immunostimulatory
  2. (1993). Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin.
  3. (1998). Analysis of cytokine production by inflammatory mouse macrophages at the single-cell level: selective impairment of IL-12 induction in Leishmania-infected cells.
  4. (1996). Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ.
  5. (1988). Cutaneous host defense in leishmaniasis: interaction of isolated dermal macrophages and epidermal Langerhans cells with the insect-stage promastigote.
  6. (1998). Cytokines induce the development of functionally heterogeneous T helper cell subsets.
  7. (1998). Dendritic cells and the control of immunity.
  8. (1995). Dendritic cells in Leishmania major-immune mice harbor persistent parasites and mediate an antigen-specific T cell immune response.
  9. (1998). Dendritic cells, but not macrophages, produce IL-12 immediately following Leishmania donovani infection.
  10. (1997). E-cadherinmediated adhesion involving Langerhans cell-like dendritic cells expanded from murine fetal skin.
  11. (1991). Experimental leishmaniasis in humans: review.
  12. (1997). Genetic control of interleukin 12 responsiveness: implications for disease pathogenesis.
  13. (1996). High level IL12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
  14. (1997). In vivo microbial stimulation induces rapid CD40 ligand–independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas.
  15. (1993). Interleukin 12 and tumor necrosis factor a are costimulators of interferon g production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist.
  16. (1993). Interleukin 12 is required for the T-lymphocyteindependent induction of interferon g by an intracellular parasite and induces resistance in T-cell-deficient hosts.
  17. (1995). Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity.
  18. (1993). Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigenspecific T cells.
  19. (1997). Leishmania major: promastigotes induce expression of a subset of chemokine genes in murine macrophages.
  20. (1996). Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow–derived macrophages from susceptible and resistant mice.
  21. (1997). Metacyclogenesis modulates the ability of Leishmania promastigotes to induce IL-12 production in human mononuclear cells.
  22. (1992). Murine epidermal Langerhans cells are potent stimulators of an antigen-specific T cell response to Leishmania major, the cause of cutaneous leishmaniasis.
  23. (1993). Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major.
  24. (1998). Regulation of E-cadherinmediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo.
  25. (1997). Synthesis, stability, and subcellular distribution of major histocompatibility complex class II molecules in Langerhans cells infected with Leishmania major.
  26. (1991). The dendritic cell system and its role in immunogenicity.
  27. (1997). The fate and persistence of Leishmania major in mice of different genetic backgrounds: an example of exploitation of the immune system by intracellular parasites.
  28. (1995). The Immune Functions of Epidermal Langerhans Cells.
  29. (1998). The immune response to Leishmania: mechanisms of parasite control and evasion.
  30. (1995). The regulation of immunity to Leishmania major.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.