Interleukin 17A Acts Synergistically With Interferon gamma to Promote Protection Against Leishmania infantum Infection

Interleukin 17 (IL-17) is an inflammatory cytokine that plays a protective role against intracellular parasites. The role of IL-17 during Leishmania infection remains controversial and poorly defined. We evaluated whether IL-17 participates in the host immune response to Leishmania infantum. IL-17A is present in sera from patients with visceral leishmaniasis and decreases after successful treatment. In C57BL/6 infected mice, higher production of IL-17A coincided with the peak of parasitism gamma Il17ra(-/-) mice were more susceptible to infection and also exhibited reduced inflammatory infiltration and interferon gamma (IFN-gamma)-expressing CD4(+) T-cell frequencies than wild-type mice. The frequencies of FoxP3(+)CD4(+) T cells and interleukin 10 (IL-10)-expressing CD4(+) T cells were increased in Il17ra(-/-) mice. We also demonstrated that IL-17A acts synergistically with IFN-gamma to potentiate NO production and leishmanicidal activity in infected macrophages. Therefore, our results indicate that L. infantum induces IL-17A production, which promotes the control of parasite replication by strengthening T-helper type 1 responses and NO production and prevents regulatory T-cell and IL-10-expressing T-cell expansion. (AU)