Inflammatory Ly6Chigh Monocytes Protect against Candidiasis through IL-15-Driven NK Cell/Neutrophil Activation
Inflammatory Ly6Chigh Monocytes Protect against Candidiasis through IL-15-Driven NK Cell/Neutrophil Activation
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DOI：
10.1016/j.immuni.2017.05.009
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发表时间：
2017-06-20
期刊：
影响因子：
32.4
通讯作者：
Ardavin, Carlos
中科院分区：
文献类型：
--
作者：
Dominguez-Andres, Jorge;Feo-Lucas, Lidia;Ardavin, Carlos
中性粒细胞在防御系统性念珠菌病中起着至关重要的作用，系统性念珠菌病是一种与接受免疫抑制治疗的患者的高死亡率相关的疾病，尽管促进中性粒细胞杀念珠菌活性的早期免疫机制仍有待深入研究。在这里，我们使用系统性念珠菌病的小鼠模型来探索炎症性Ly 6C（高）单核细胞在抗念珠菌先天免疫反应期间NK细胞介导的中性粒细胞活化中的作用。白色念珠菌我们发现有效的抗念珠菌免疫需要脾和肾之间的协同反应，这依赖于脾炎症Ly 6C（高）单核细胞产生的I型干扰素依赖性IL-15，以驱动脾NK细胞的有效激活和GM-CSF释放;这反过来又是增强肾中性粒细胞的念珠菌杀伤潜力所必需的。我们的研究结果揭示了IL-15作为防御系统性念珠菌病的关键介质的作用，并为基于IL-15的抗真菌免疫疗法的设计带来了希望。
Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C(high) monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C(high) monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils. Our findings unveil a role for IL-15 as a critical mediator in defense against systemic candidiasis and hold promise for the design of IL-15-based antifungal immunotherapies.