Vagal Regulation of Group 3 Innate Lymphoid Cells and the Immunoresolvent PCTR1 Controls Infection Resolution.
Vagal Regulation of Group 3 Innate Lymphoid Cells and the Immunoresolvent PCTR1 Controls Infection Resolution.
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第3组先天淋巴样细胞和免疫反应PCTR1的迷走神经调节可控制感染。
DOI：
10.1016/j.immuni.2016.12.009
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发表时间：
2017-01-17
期刊：
影响因子：
32.4
通讯作者：
Serhan CN
中科院分区：
文献类型：
--
作者：
Dalli J;Colas RA;Arnardottir H;Serhan CN
揭示在细菌感染的解决中控制免疫反应的机制对于开发解决感染性炎症而没有不必要的副作用的新治疗策略至关重要。在此，我们发现，小鼠迷走神经系统的破坏延迟大肠杆菌感染的解决。剥离右侧迷走神经减少了腹膜组3先天性淋巴样细胞（ILC3）的数量，并改变了腹膜巨噬细胞的反应。迷走神经切断术导致炎症性腹膜脂质介质分布，其特征在于消退素浓度降低，包括保护性免疫消退剂PCTR 1，沿着升高的炎症引发类花生酸。我们发现，乙酰胆碱上调ILC3的PCTR生物合成途径。给切断迷走神经的小鼠施用PCTR1或ILC3可恢复组织分辨张力和宿主对E.大肠杆菌感染。这些发现一起阐明了由ILC3衍生的前分辨回路（包括PCTR1）介导的宿主保护机制，其由局部神经元输出控制以调节组织分辨张力和骨髓细胞反应。对感染的炎症反应的消退对于防止对宿主的损害是重要的。Dalli等人发现迷走神经通过调节组织ILC3数量和上调保护性介质PCTR1来促进细菌清除，所述保护性介质PCTR1调节腹膜巨噬细胞反应并促进感染的消退。
Uncovering mechanisms that control immune responses in the resolution of bacterial infections is critical for the development of new therapeutic strategies that resolve infectious-inflammation without unwanted side effects. Herein, we found that disruption of the vagal system in mice delayed resolution of Escherichia coli infection. Dissection of the right vagus decreased peritoneal Group 3 innate lymphoid cell (ILC3) numbers and altered peritoneal macrophage responses. Vagotomy resulted in an inflammatory peritoneal lipid mediator profile characterized by reduced concentrations of resolvins, including the protective immunoresolvent PCTR1, along with elevated inflammation-initiating eicosanoids. We found that acetylcholine upregulated the PCTR biosynthetic pathway in ILC3s. Administration of PCTR1 or ILC3s to vagotomised mice restored tissue resolution tone and host responses to E. coli infections. Together these findings elucidate a host protective mechanism mediated by ILC3-derived pro-resolving circuit, including PCTR1, that is controlled by local neuronal output to regulate tissue resolution tone and myeloid cell responses. Resolution of the inflammatory response to infections is important for preventing damage to the host. Dalli et al. find that the vagus nerve promotes bacterial clearance by regulating tissue ILC3 numbers and upregulating the protective mediator PCTR1, which conditions peritoneal macrophage responses and promotes resolution of infection.