Cytokines in leishmaniasis: a complex network of stimulatory and inhibitory interactions

Abstract

The work of immunologists, cell biologists and parasitologists in the field of leishmaniasis has not only provided important insights into the immunopathogenesis of this disease, but also yielded fundamental contributions to our understanding of basic immunological phenomena and of host-parasite interactions. The ability of recombinant interferon-gamma to induce the microbicidal activity of phagocytes and the opposite effect of inhibitory cytokines was first demonstrated with Leishmania-infected macrophages. The selective development of protective and disease-mediating CD4+ T lymphocytes as well as their differential influence on the course of the disease has been long investigated in the murine Leishmania major model and now represents one of the best examples for the in vivo induction of type 1 versus type 2 T helper lymphocytes. At the same time, this model has also been extensively used for immunization studies and cytokine therapy, which shed light on the functions of cytokines in vivo as well as on the mechanism(s) of disease resistance and susceptibility. In this review we will discuss the present picture of the cytokine network in murine L. major infections.