Interleukin-15, as interferon-gamma, induces the killing of Leishmania infantum in phorbol-myristate-acetate-activated macrophages increasing interleukin-12

Abstract

The potential leishmanicidal activity of interleukin-15 (IL-15) was examined while priming with the cytokine phorbol-myristate-acetate (PMA)-activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL-15 determined a significant antileishmanial activity, comparable with that induced by interferon-gamma (IFN-γ). The killing of Leishmania in macrophages primed with IL-15, as well as with IFN-γ, was followed by an increase in the IL-12 synthesis. The neutralization of IL-15 or IFN-γ, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA-activated macrophages, the neutralization of IL-12 production by a specific anti-IL-12 MoAb reduced leishmanicidal activity induced by IL-15 and IFN-γ. Data indicate that IL-15 could have a role as an activator of leishmanicidal activity, directly or indirectly, by inducing IL-12 production.