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.
