Skin dendritic cells in murine cutaneous leishmaniasis

Studies of the immunopathogenesis of Leishmania major-induced murine cutaneous leishmaniasis provide a framework for understanding the evolution of L. major infection of skin in humans and the foundation for rationale vaccine design. Experiments in which infection is initiated with "supraphysiologic" numbers of parasites clearly identify Th-derived type I cytokines as essential participants in macrophage activation and macrophage nitric oxide production as prerequisite for parasite control. Dendritic cells, rather than macrophages, appear to be responsible for L. major-specific Th priming in these studies. Recent studies of murine cutaneous leishmaniasis in a model system in which infection is initiated with lower, more physiologic numbers of parasites confirm many of the important findings obtained in "high dose" inoculation models, but important differences have been noted. The low dose inoculation model should ultimately provide insights into mechanisms that are responsible for dendritic cell recruitment into leishmania lesions, mechanisms that facilitate parasite acquisition by skin dendritic cells and cellular interactions that eventuate in T cell priming and lesion involution.