Langerhans Cell Migration in Murine Cutaneous Leishmaniasis: Regulation by Tumor Necrosis Factor α Interleukin-1β, and Macrophage Inflammatory Protein-1α

After intradermal infection of mice with the obligatory intracellular parasite Leishmania major, Langerhans cells (LC) are intimately involved in the induction of the primary T-cell immune response. LC can phagocytose Leishmania and transport ingested parasites from the infected skin to the regional lymph nodes. Since TNFα and IL-1β have been shown to induce LC migration after epicutaneous exposure to skin-sensitizing chemicals, we investigated the involvement of both cytokines in the migration of Leishmania-infected LC. In addition, the relevance of two chemokines of the β subfamily, macrophage inflammatory protein 1α(MIP-1α) and macrophage chemoattractant protein 1 (MCP-1), was analyzed.In vivo depletion of TNFα significantly reduced the amount of infected LC and the parasite load in the draining lymph nodes. Administration of recombinant TNFα caused the reverse effect. In contrast, the depletion of IL1β enhanced the parasite-induced LC migration, whereas treatment with recombinant IL-1β, as well as recombinant MIP- c, reduced the rate of infected LC in the lymph nodes. MCP- did not influence LC migration. Our data demonstrate that TNFα and IL-1β are regulating the LCmediated transport of Leishmania and also provide evidence for the involvement of macrophage attractant chemokines in this process.