Langerhans cell migration in murine cutaneous leishmaniasis: regulation by tumor necrosis factor alpha, interleukin-1 beta, and macrophage inflammatory protein-1 alpha.

Jörg Arnoldi,Heidrun Moll

doi:10.1155/1998/21095

Abstract

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.

Highlights

Epidermal Langerhans cells (LC), as members of the dendritic-cell lineage, are part of a system of potent antigen-presenting cells in skin and lymph nodes (Steinman, 1991)
It is of particular importance that at this early time point, Leishmania parasites only can be found in lymph node dendritic cells and are not associated with macrophages (Moll et al, 1993)
In order to confirm the involvement of TNFce in the induction of LC migration, mice were treated with neutralizing antiTNFce antibodies, 2 hr before infection with the parasite

Summary

INTRODUCTION

Epidermal Langerhans cells (LC), as members of the dendritic-cell lineage, are part of a system of potent antigen-presenting cells in skin and lymph nodes (Steinman, 1991). MOLL lymphatics into the lymph nodes, draining the site of epicutaneous exposure (Macatonia et al, 1987; Larsen et al, 1990) During this migration, LC are subject to a functional and phenotypic differentiation that is thought to be initiated by epidermal cytokines. LC are subject to a functional and phenotypic differentiation that is thought to be initiated by epidermal cytokines They develop into highly efficient antigen-presenting cells with the potential to induce the primary stimulation of specific T cells. Recent studies revealed that the induction of an antigen-specific T-cell immune response after cutaneous infection with the obligatory intracellular parasite Leishmania major is mediated by epidermal LC (Moll et al, 1993, 1995). To distinguish the effects of locally produced mediators from those of exogenous sources on LC migration, we used a skin explant culture system

RESULTS

DISCUSSION

MATERIAL AND METHODS