IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages
IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages
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DOI：
10.1002/eji.201343493
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发表时间：
2013-10-01
影响因子：
5.4
通讯作者：
Hisaeda, Hajime
中科院分区：
文献类型：
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作者：
Ishida, Hidekazu;Imai, Takashi;Hisaeda, Hajime
尽管 IL-12 被认为有助于保护性免疫反应，但 IL-23（IL-12 家族成员）在疟疾中发挥的作用尚不清楚。在这里，我们发现 IL-23 是在伯氏疟原虫 NK65 感染过程中产生的。 IL-23 (p19KO) 缺陷的小鼠比野生型 (WT) 对照小鼠的寄生虫血症更高且死亡更早。有趣的是，p19KO 小鼠产生 IL-17 的脾细胞数量低于 WT 小鼠。此外，缺乏 IL-17 (17KO) 的小鼠比 WT 对照小鼠遭受更高的寄生虫血症，表明 IL-23 介导的保护依赖于感染期间 IL-17 的诱导。我们发现巨噬细胞负责响应 IL-23 产生 IL-17。我们观察到 p19KO 和 17KO 小鼠的脾巨噬细胞显着减少，这两种小鼠都变得非常容易受到感染。因此，IL-17 似乎对于维持脾巨噬细胞至关重要。将巨噬细胞过继转移到巨噬细胞耗尽的小鼠体内证实了巨噬细胞衍生的 IL-17 是受体小鼠中巨噬细胞积累和寄生虫根除所必需的。我们还发现 IL-17 诱导 CCL2/7，从而招募巨噬细胞。我们的研究结果揭示了一种新的保护机制，IL-23、IL-17 和巨噬细胞可降低血期疟疾寄生虫感染的严重程度。
Although IL-12 is believed to contribute to protective immune responses, the role played by IL-23 (a member of the IL-12 family) in malaria is elusive. Here, we show that IL-23 is produced during infection with Plasmodium bergheiNK65. Mice deficient in IL-23 (p19KO) had higher parasitemia and died earlier than wild-type (WT) controls. Interestingly, p19KO mice had lower numbers of IL-17-producing splenic cells than their WT counterparts. Furthermore, mice deficient in IL-17 (17KO) suffered higher parasitemia than the WT controls, indicating that IL-23-mediated protection is dependent on induction of IL-17 during infection. We found that macrophages were responsible for IL-17 production in response to IL-23. We observed a striking reduction in splenic macrophages in the p19KO and 17KO mice, both of which became highly susceptible to infection. Thus, IL-17 appears to be crucial for maintenance of splenic macrophages. Adoptive transfer of macrophages into macrophage-depleted mice confirmed that macrophage-derived IL-17 is required for macrophage accumulation and parasite eradication in the recipient mice. We also found that IL-17 induces CCL2/7, which recruit macrophages. Our findings reveal a novel protective mechanism whereby IL-23, IL-17, and macrophages reduce the severity of infection with blood-stage malaria parasites.