Presentation of Skin-Derived Leishmania Antigen by Dendritic Cell Subtypes

The tropical disease leishmaniasis is initiated by flagellated parasites of the genus Leishmania (L.), which are inoculated into the skin during the blood meal of a sandfly vector. A broad spectrum of clinical manifestations in humans, ranging from a self-limiting cutaneous infection to disseminating visceral leishmaniasis, are described with respect to the transmitted Leishmania species. During the last decades the experimental model of leishmaniasis, in which mice are infected with stationary phase promastigote parasites, allowed the examination of many immunological details of the hostparasite interaction. For instance, it is shown that the obligatory intracellular Leishmania parasites need phagocytic cells for replication as soon as the parasites are located in the dermal compartment. In this regard, neutrophils and macrophages play a pivotal role as host cells for Leishmania replication. On the other hand, infected macrophages produce leishmanicidal molecules after appropriate activation by antigen-specific T helper (h) cells. Thus, healing of leishmaniasis is associated with a protective Th1-type response, characterized by an early interferon-γ production by CD4+ T cells and the expression of inducible nitric oxide synthase by activated macrophages. In this context, it is generally accepted that professional antigen presenting cells are crucial for the induction of the protective Th1-type response in skin-draining lymph nodes. Due to the fact that L. major parasites enter the body via the skin, epidermal Langerhans Cells (LCs) were thought to be responsible for the initiation of the adaptive T cell-mediated immunity. More recent data indicate that dermal Dendritic Cells (DCs), rather than epidermal LCs, might be important for the initiation of the adaptive immune response. However, an indirect role for migratory skin-derived epidermal LCs in T cell-mediated immunity, possibly in delivering skin-derived antigens to cutaneous lymph node-resident DCs, could not be excluded in general. Based on the current knowledge about the role of DC subsets in experimental leishmaniasis, it is feasible that distinct DC subtypes interact with particular T cell populations: LCs with “regulatory” T cells, Langerin+ DCs with CD8+ T cells, and Langerin- DCs with CD4+ T cells.