CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis

Eur J Immunol. 2004 Jun;34(6):1542-50. doi: 10.1002/eji.200324586.

Abstract

In the early phase of leishmaniasis three types of potential antigen-presenting cells, including epidermal Langerhans cells (LC), dermal dendritic cells (DC) and inflammatory DC, are localized at the site of infection. Therefore, it has been a central question which cell type is responsible for the initiation of a protective immune response. In the early stage of an anti-Leishmania immune response, detectable Leishmania major antigen was localized in the paracortex of the draining lymph nodes (LN). Characterization of antigen-positive cells showed that L. major co-localized with DC of a CD11c(+) CD8 alpha(-) Langerin(-) phenotype. To determine the area of antigen uptake, dermis or epidermis, and to further define the type of antigen-transporting cells, L. major was inoculated subcutaneously and concurrently LC were mobilized with fluorescein isothiocyanate (FITC). After 3 days, DC carrying L. major antigen were always FITC(-), indicating a dermal and not an epidermal origin. Moreover, addition of L. major antigen to ex vivo isolated CD8 alpha(-) and CD8 alpha(+) DC from the draining LN of L. major-infected C57BL/6 mice demonstrated that both DC subpopulations were able to stimulate antigen-specific T cell proliferation in vitro. Without addition of exogenous antigen only the CD8 alpha(-) Langerin(-) DC were capable of stimulating antigen-specific T cell proliferation. Thus, we demonstrate that CD8 alpha(-) Langerin(-) DC and not LC are the basis of the protective immune response to intracellular L. major parasites in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens, Protozoan / immunology
  • Antigens, Protozoan / metabolism
  • Antigens, Surface / biosynthesis
  • Antigens, Surface / immunology*
  • CD8 Antigens / biosynthesis
  • CD8 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / parasitology
  • Cell Division / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate / chemistry
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology*
  • Langerhans Cells / parasitology
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / immunology*
  • Leishmania major / genetics
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / parasitology
  • Mannose-Binding Lectins / biosynthesis
  • Mannose-Binding Lectins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • RNA, Protozoan / chemistry
  • RNA, Protozoan / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / immunology
  • Skin / metabolism
  • Skin / parasitology

Substances

  • Antigens, Protozoan
  • Antigens, Surface
  • CD8 Antigens
  • CD8alpha antigen
  • Cd207 protein, mouse
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • RNA, Protozoan
  • Fluorescein-5-isothiocyanate