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

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.