CD8α- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis

Authors

  • Uwe Ritter,

    1. Nachwuchsgruppe 1, Interdisziplinäres Zentrum für Klinische Forschung der Universität Erlangen-Nürnberg, Erlangen, Germany
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  • Anja Meißner,

    1. Nachwuchsgruppe 1, Interdisziplinäres Zentrum für Klinische Forschung der Universität Erlangen-Nürnberg, Erlangen, Germany
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  • Christina Scheidig,

    1. Nachwuchsgruppe 1, Interdisziplinäres Zentrum für Klinische Forschung der Universität Erlangen-Nürnberg, Erlangen, Germany
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  • Heinrich Körner

    Corresponding author
    1. Nachwuchsgruppe 1, Interdisziplinäres Zentrum für Klinische Forschung der Universität Erlangen-Nürnberg, Erlangen, Germany
    2. Comparative Genomics Centre, James Cook University, Townsville, Australia
    • Comparative Genomics Centre, Molecular Sciences Bld. 21, James Cook University, Townsville, Qld 4811, Australia Fax: +61-7-4781-6078
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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 localizedat 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+ CD8α 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 antigenwere always FITC, indicating a dermal and not an epidermal origin. Moreover, addition of L. major antigen to ex vivo isolated CD8α and CD8α+ DC fromthe 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 CD8α Langerin DC were capable of stimulating antigen-specific T cell proliferation. Thus, we demonstrate that CD8α Langerin DC and not LC are the basis of the protective immune response to intracellular L. major parasites in vivo.

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