Monocyte-Derived Dendritic Cells Perform Hemophagocytosis to Fine-Tune Excessive Immune Responses
Monocyte-Derived Dendritic Cells Perform Hemophagocytosis to Fine-Tune Excessive Immune Responses
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DOI：
10.1016/j.immuni.2013.06.019
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发表时间：
2013-09-19
期刊：
影响因子：
32.4
通讯作者：
Ohteki, Toshiaki
中科院分区：
文献类型：
--
作者：
Ohyagi, Hideaki;Onai, Nobuyuki;Ohteki, Toshiaki
由于免疫反应同时防御和伤害宿主，因此必须精细调节免疫系统以确保宿主的存活。在这里，我们已经表明，当注射高Toll样受体配体剂量或感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）克隆13，它具有高病毒周转，炎性单核细胞衍生的树突状细胞（Mo-DCs）吞噬凋亡的红系细胞。在这个过程中，称为噬血作用，磷脂酰丝氨酸（PS）作为一个“吃我”的信号。I型干扰素对于PS暴露于红系细胞和PS受体在Mo-DCs中的表达都是必需的。重要的是，噬血细胞作用是从Mo-DC产生白细胞介素-10（IL-10）所必需的。阻断噬血细胞作用或Mo-DC衍生的IL-10显著增加病毒感染宿主的细胞毒性T细胞淋巴细胞活性、组织损伤和死亡率，表明噬血细胞作用调节免疫应答以确保宿主在体内的存活。这揭示了严重炎症和感染性疾病中噬血细胞作用的生理相关性。
Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic T cell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival in vivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.