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

神经/免疫/行为相互作用：寄生虫的机制、功能和利用

• 批准号: RGPIN-2018-04037
• 负责人: Adamo, Shelley
• 金额: $ 3.42万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=643446
• 关键词: Neural; Immune; Behavioural; interactions; Mechanisms

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.

动物，包括人类，有时会抑制它们抵抗疾病的能力。这种抑制经常被认为是功能失调的，尽管它存在于整个门的动物中，并且是通过类似的分子途径诱导的。我提出了一个新颖的建议，即这些变化反映了免疫系统的重新配置。这种重组可能不会产生最大的抗病能力，但当资源被转移到其他生理系统(例如，战斗或逃跑或繁殖)时，它可以产生最好的保护水平。*为了验证这一假设，我和我的学生们将研究捕食者压力对毛毛虫Manduca sexta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，这种状态是否对维持疾病抵抗力很重要。我们将测试在慢性捕食者应激期间，当应激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，我们将使用成年雌性蟋蟀(Gryllus Texensis)来测试随着年龄的增长，向更促炎状态的转变是否会提高繁殖成功。我们将评估谷胱甘肽--昆虫体内的一种重要抗氧化剂--是否处于生殖和免疫功能之间生理平衡的中心。衰老前免疫功能与年龄相关的变化可能反映出从自我维持到生殖的转变。*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)，以支持我们关于免疫-神经网络一体化的假说。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，浆细胞扩散肽，是否影响六分枝杆菌大脑的神经功能。我们的研究将首次证明昆虫细胞因子影响神经活动。*该提议的新颖性和预期影响。我们将使用先进的统计技术(例如结构方程模型)来整合我们的行为、生理、生化和基因组数据。这种整合将使人们有可能展示神经-免疫相互作用如何以及为什么会有益，即使疾病抵抗力似乎降低了。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。这将引起广泛的生物学家(例如行为生理学家、行为生态学家和生态免疫学家)的兴趣。这项研究还有可能具有实际意义，因为它提高了长时间促炎状态可能有价值的可能性。