Neural/Immune/Behavioural interactions: Mechanisms, functions and exploitation by parasites

动物，包括人类，有时会抑制自己抵抗疾病的能力。这种抑制通常被认为是功能失调的，尽管它存在于跨门的动物中，并且是通过相似的分子途径诱导的。我提出了一个新颖的建议，这些变化反映了免疫系统的重新配置。这种重新配置可能不会产生最大的抗病能力，但当资源被分流到其他生理系统（例如战斗或逃跑或繁殖）时，它会产生可能的最佳保护水平。***为了验证这个假设，我和我的学生将研究捕食者的压力对毛虫免疫系统的影响。我们将量化向促炎状态的转变，并测试当应激反应被激活时，这种状态对维持疾病抵抗力是否重要。我们将测试在慢性捕食者压力下，当压力引起的免疫系统变化被阻止时，疾病抵抗力是否会进一步降低。***此外，我们将使用成年雌蟋蟀（Gryllus texensis）来测试是否随着年龄的增长而转向更促炎的状态会提高繁殖成功率。我们将评估谷胱甘肽，昆虫中重要的抗氧化剂，是否在繁殖和免疫功能之间的生理权衡中处于中心地位。在衰老之前，与年龄相关的免疫功能变化可能反映了从自我维持到繁殖的转变。***最后，我们将测试昆虫免疫系统是否向神经系统发送化学信号（即细胞因子），以支持我们的综合免疫-神经网络假设。我们将利用一些寄生虫通过改变宿主细胞因子的产生来改变宿主行为的能力来证明这种联系。我们将测试昆虫细胞因子，即浆细胞扩张肽，是否影响sexta的大脑神经功能。我们的研究将首次证明昆虫细胞因子会影响神经活动。******提案的新颖性和预期影响。我们将使用先进的统计技术（如结构方程模型）来整合我们的行为，生理，生化和基因组数据。这种整合将有可能展示神经免疫相互作用是如何以及为什么有益的，即使抗病能力似乎降低了。这项研究将通过展示生理网络的重新配置如何为看似不适应的连接提供解释，从而提供重大进展。这将是广泛的生物学家（如行为生理学家，行为生态学家和生态免疫学家）的兴趣。这项研究也有可能具有实际意义，因为它提高了延长促炎状态可能具有价值的可能性。

Animals, including humans, sometimes suppress their ability to resist disease. This suppression is frequently considered dysfunctional, even though it exists in animals across phyla, and is induced using similar molecular pathways. I make the novel suggestion that these changes reflect a reconfiguration of the immune system. This reconfiguration may not produce maximal disease resistance, but it produces the best level of protection possible when resources are shunted towards other physiological systems (e.g. fight-or-flight or reproduction). *** To test this hypothesis, my students and I will examine the effects of predator stress on the immune system of the caterpillar, Manduca sexta. We will quantify the shift to a pro-inflammatory state, and test whether this state is important for maintaining disease resistance when stress responses are activated. We will test whether disease resistance during chronic predator stress is reduced even further when stress-induced changes on the immune system are prevented.*** In addition, we will use adult female crickets (Gryllus texensis) to test whether a shift to a more pro-inflammatory state with age enhances reproductive success. We will assess whether glutathione, an important antioxidant in insects, is at the centre of a physiological trade-off between reproduction and immune function. Age-related changes in immune function prior to senescence may reflect a shift away from self-maintenance and towards reproduction.*** Finally, we will test whether insect immune systems send chemical signals (i.e. cytokines) to the nervous system, to support our hypothesis of an integrated immune-neural network. We will use the ability of some parasites to change host behaviour by altering host cytokine production to demonstrate this connection. We will test whether the insect cytokine, plasmatocyte spreading peptide, affects neural function in the brain of M. sexta. Our study will be the first to demonstrate that an insect cytokine affects neural activity.******Novelty and Expected Impact of the Proposal. We will use advanced statistical techniques (e.g. structural equation models) to integrate our behavioural, physiological, biochemical, and genomic data. This integration will make it possible to show how and why neural-immune interactions can be beneficial, even if disease resistance appears to be reduced. This research will provide a significant advance by demonstrating how reconfiguration of physiological networks can provide an explanation for seemingly maladaptive connections. It will be of interest to a broad range of biologists (e.g. behavioural physiologists, behavioural ecologists and ecoimmunologists). This research also has the potential to be of practical importance, by raising the possibility that prolonged pro-inflammatory states could have value.