Interleukin‐2‐Activated Natural Killer Cells May Have a Direct Role in the Control of Leishmania (Leishmania) amazonensis Promastigote and Macrophage Infection

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Abstract
To study the role of Natural Killer (NK) cells in Leishmania infection, peritoneal macrophages from BALB/c mice were infected with Leishmania (Leishmania) amazonensis promastigotes and incubated with interleukin‐2 (IL‐2)‐activated NK (A‐NK) cells at different ratios of A‐NK cells to infected macrophages (5:1, 1:1, 0.2:1). The A‐NK cells were added either together with the parasites (0‐h group) or 24 h later (24‐h group). Morphological studies of the cultures revealed predominance of parasitic debris within macrophages that were in close contact with A‐NK cells and the decrease in parasite recovery was directly proportional to the A‐NK cell concentration used. Interferon‐γ (IFN‐γ) and IL‐12 were detected in the supernatant at levels proportional to the A‐NK cell concentration used. No significant difference was observed between the groups with respect to NO levels in the culture supernatant. When A‐NK cells were added directly to the L. (L.) amazonensis promastigote cultures, the parasite recovery decreased proportional to the number of A‐NK cells added. In vivo studies demonstrated smaller lesion sizes in animals inoculated with both parasites and A‐NK cells compared with parasites alone. Histopathology of the skin lesions from animals receiving A‐NK cells together with the parasites showed moderate parasitism and a nodular inflammatory infiltrate formed by mononuclear cells and a few vacuolized macrophages. In contrast, animals inoculated only with the parasites showed a highly parasitized dermis with infiltration of intensely vacuolized macrophages. These results demonstrate the role of A‐NK cells in parasite lysis and in resistance of macrophages to L. (L.) amazonensis in the early phase of infection.

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