The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response

Abstract

The complicated interactions between Leishmania and the host antigen-presenting cells (APCs) have fundamental effects on the final outcome of the disease. Two major APCs, macrophages and dendritic cells (DCs), play critical roles in mediating resistance and susceptibility during Leishmania infection. Macrophages are the primary resident cell for Leishmania: they phagocytose and permit parasite proliferation. However, these cells are also the major effector cells to eliminate infection. The effective clearance of parasites by macrophages depends on activation of appropriate immune response, which is usually initiated by DCs. Here, we review the early interaction of APCs with Leishmania parasites and how these interactions profoundly impact on the ensuing adaptive immune response. We also discuss how the current knowledge will allow further refinement of our understanding of the interplay between Leishmania and its hosts that leads to resistance or susceptibility.

Keywords: cytokines; dendritic cells; innate immunity; macrophages; parasitic-protozoan; rodents.

Figure 1

Dendritic cells and macrophages regulate the outcome of Leishmania infection. Following infection, both macrophages and dendritic cells phagocytose Leishmania leading to different functional outcomes. Infected dendritic cells produce IL-12, which is critical for the development of IFN-γ-producing CD4⁺ Th1 cells. IFN-γ acts on infected macrophages leading to their activation (classical activation), upregulation of iNOS, and production of nitric oxide and other free radicals that are important for intracellular parasite killing. In contrast, the production of IL-4 by other cell types (including keratinocytes and Vβ4 T cells) supports CD4⁺ Th2 development. Th2 cells produce IL-4 and IL-13, which leads to upregulation of arginase activity, alternative macrophage activation and the production polyamines that favor intracellular parasite proliferation. In addition, naturally occurring regulatory T cells (Treg) and infected macrophages also produce some immunoregulatory cytokines including IL-10 and TGF-β, which further deactivate infected cells leading to impaired parasite killing.