Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells.
Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells.
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DOI：
10.1371/journal.ppat.1003787
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
McMullan R
中科院分区：
文献类型：
--
作者：
Anderson A;Laurenson-Schafer H;Partridge FA;Hodgkin J;McMullan R
神经系统和免疫系统相互影响，使动物能够迅速保护自己免受内部和外部环境的变化。然而，这些系统在哺乳动物中的复杂性质使得很难确定神经元信号如何影响免疫反应。在这里，我们表明，5-羟色胺，秀丽隐杆线虫化学感觉神经元合成，调节免疫反应。从这些细胞释放的血清素直接或间接地调节上皮细胞中的G蛋白信号传导。这些细胞中的信号传导是对天然病原体嗜热微杆菌感染的免疫应答所必需的。在这里，我们表明，5-羟色胺信号抑制先天免疫反应，并限制病原体清除率。我们证明了C.秀丽线虫使用经典的神经递质来改变免疫反应。从感觉神经元释放的5-羟色胺可以起作用以响应动物的外部环境的变化（例如食物的可用性或质量）来修改免疫系统。神经和免疫系统对环境的变化做出快速而准确的反应。这些系统之间的交流可能是抑郁症等神经系统疾病的基础，并解释了为什么环境因素，如心理压力，增加了感染的易感性。连接神经系统和免疫系统的分子机制是什么？C.秀丽线虫有一个很好的神经系统，可以被几种病原体感染，使其成为解决这个问题的适当模式生物。我们发现，在暴露于环境中的感觉神经元中，神经递质5-羟色胺的合成改变了对嗜热微杆菌感染的易感性。与铜绿假单胞菌感染不同的是，在铜绿假单胞菌感染中，5-羟色胺信号传导是行为回避所必需的，而在铜绿假单胞菌感染中，5-羟色胺信号传导通过调节上皮细胞中的G蛋白信号传导途径来抑制免疫反应。因此，我们表明，改变血清素水平可以根据环境触发不同的结果。我们确定了一个单一的神经元能够修改免疫反应，并证明C。秀丽线虫使用经典的神经递质来改变其免疫力。我们的工作表明C. elegans可用于研究神经递质和免疫反应之间的相互串扰，这可能对包括抑郁症在内的疾病的病理学很重要。
The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food. The nervous and immune systems respond quickly and precisely to changes in the environment. Communication between these systems may underlie neurological disorders such as depression, and explain why environmental factors, such as psychological stress, increase infection susceptibility. What are the molecular mechanisms that link the nervous and immune systems? C. elegans has a well described nervous system and can be infected by several pathogens, making it an appropriate model organism with which to address this question. We show that synthesis of the neurotransmitter serotonin, in sensory neurons exposed to the environment, alters susceptibility to infection with Microbacterium nematophilum. Unlike infection with Pseudomonas aeruginosa, where serotonin signaling is required for behavioral avoidance, here serotonin signaling suppresses the immune response by regulating a G-protein signaling pathway in epithelial cells. Thus, we show that altering levels of serotonin can trigger different outcomes depending on the environment. We identify a single neuron capable of modifying the immune response and demonstrate that C. elegans uses classical neurotransmitters to modify its immunity. Our work demonstrates that C. elegans can be used to study reciprocal cross talk between neurotransmitters and immune responses that may be important for the pathology of disorders including depression.
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DOI：
10.1523/jneurosci.1692-11.2011
发表时间：
2011-06-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jafari G;Xie Y;Kullyev A;Liang B;Sze JY
通讯作者：
Sze JY
影响因子：
4
作者：
Ahern, Gerard P.
通讯作者：
Ahern, Gerard P.
影响因子：
56.9
作者：
HORVITZ, HR;CHALFIE, M;EVANS, PD
通讯作者：
EVANS, PD
影响因子：
10.5
作者：
Hajdu-Cronin, YM;Chen, WJ;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
--
作者：
AVERY, L;HORVITZ, HR
通讯作者：
HORVITZ, HR