Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner.
Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner.
复制标题
神经对多巴胺能信号传导的抑制可增强细胞非自治方式的免疫力。
DOI：
10.1016/j.cub.2016.06.036
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发表时间：
2016-09-12
期刊：
影响因子：
--
通讯作者：
Aballay A
中科院分区：
文献类型：
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作者：
Cao X;Aballay A
先天免疫系统是宿主防御微生物感染的第一线，但其快速和不受控制的激活引发了具有有害影响的杀微生物机制。越来越多的证据表明，后生动物神经系统对来自内部和外部环境的刺激都有反应，它不仅是控制微生物杀灭途径的调节装置，也是控制细胞稳态机制的调节装置。在这里，我们报道了多巴胺信号通过d1样多巴胺受体dop4在秀丽隐杆线虫中控制先天免疫反应。氯丙嗪抑制神经系统DOP-4激活杀微生物PMK-1/p38丝裂原激活的蛋白激酶信号通路，增强宿主对细菌感染的抗性。多巴胺的免疫抑制功能起源于CEP神经元，下游的ASG神经元需要激活dop4。我们的研究结果表明，来自神经系统的多巴胺信号以细胞非自主的方式控制免疫，并将多巴胺能系统确定为潜在的治疗靶点，不仅适用于传染性疾病，还适用于由于免疫反应失调而产生的一系列疾病。
The innate immune system is the frontline of host defense against microbial infections, but its rapid and uncontrolled activation elicits microbicidal mechanisms that have deleterious effects. Increasing evidence indicates that the metazoan nervous system, which responds to stimuli originating from both the internal and the external environment, functions as a modulatory apparatus that controls not only microbial killing pathways but also cellular homeostatic mechanisms. Here, we report that dopamine signaling controls innate immune responses through a D1-like dopamine receptor, DOP-4, in Caenorhabditis elegans. Chlorpromazine inhibition of DOP-4 in the nervous system activates a microbicidal PMK-1/p38 mitogen-activated protein kinase signaling pathway that enhances host resistance against bacterial infections. The immune inhibitory function of dopamine originates in CEP neurons and requires active DOP-4 in downstream ASG neurons. Our findings indicate that dopamine signaling from the nervous system controls immunity in a cell non-autonomous manner and identifies the dopaminergic system as a potential therapeutic target for not only infectious diseases but also a range of conditions that arise as a consequence of malfunctioning immune responses.