How human macrophages can control the intracellular infection with Leishmania is not completely understood. IL-15 and IL-32 are cytokines produced by monocytes/macrophages that can induce antimicrobial mechanisms. Here, we evaluated the effects of recombinant human IL-15 (rhIL-15) on primary human macrophage infection and response to L. braziliensis. Priming with rhIL-15 reduced the phagocytosis of L. braziliensis and increased the killing of the parasites in monocyte-derived macrophages from healthy donors. rhIL-15 induced TNFα and IL-32 in uninfected cells. After infection, the high levels of rhIL-15-induced TNFα and IL-32 were maintained. In addition, there was an increase of NO and an inhibition of the parasite-induced IL-10 production. Inhibition of NO reversed the leishmanicidal effects of rhIL-15. Although rhIL-15 did not increase L. braziliensis-induced reactive oxygen intermediates (ROS) production, inhibition of ROS reversed the control of infection induced by rhIL-15. Treatment of the cells with rhIL-32γ increased microbicidal capacity of macrophages in the presence of high levels of vitamin D (25D3), but not in low concentrations of this vitamin. rhIL-15 together with rhIL-32 lead to the highest control of the L. braziliensis infection in high concentrations of vitamin D. In this condition, NO and ROS mediated rhIL-32γ effects on microbicidal activity. The data showed that priming of human macrophages with rhIL-15 or rhIL-32γ results in the control of L. braziliensis infection through induction of NO and ROS. In addition, rhIL-32γ appears to synergize with rhIL-15 for the control of L. braziliensis infection in a vitamin D-dependent manner.

人类巨噬细胞如何控制利什曼原虫的细胞内感染尚未完全了解。IL-15和IL-32是由单核细胞/巨噬细胞产生的细胞因子，可以诱导抗菌机制。在这里，我们评估了重组人IL-15（rhIL-15）对原代人巨噬细胞感染和对巴西乳杆菌的反应的影响。用rhIL-15引发可减少巴西乳杆菌的吞噬作用。并增加了对来自健康供体的单核细胞衍生巨噬细胞中寄生虫的杀死。rhIL-15诱导未感染细胞中的TNFα和IL-32。感染后，维持高水平的rhIL-15诱导的TNFα和IL-32。另外，NO增加并且抑制了寄生虫诱导的IL-10产生。NO的抑制逆转了rhIL-15的杀利什曼作用。尽管rhIL-15不会增加巴西乳杆菌诱导的活性氧中间体（ROS）产生，抑制ROS逆转了rhIL-15诱导的感染控制。在高水平的维生素D（25D3）存在下，用rhIL-32γ处理细胞可增强巨噬细胞的杀微生物能力，但在低浓度的这种维生素中则不能。重组人IL-15一起的rhIL-32引到L的最高控制braziliensis感染的高浓度的维生素D.在这种条件下，NO和ROS介导的对杀微生物活性的rhIL-32γ的效果。数据显示人类巨噬细胞与的rhIL-15或重组人IL-32γ导致L的控制促发braziliensis感染通过NO和ROS的诱导。此外，重组人IL-32γ似乎与重组人IL-15协同作用为L的控制braziliensis 以维生素D依赖的方式感染。