Proximate and ultimate causes of immune/behavioural interactions

免疫/行为相互作用的直接和最终原因

• 批准号: 203133-2013
• 负责人: Adamo, Shelley
• 金额: $ 1.97万
• 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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631725
• 关键词: Proximate; ultimate; causes; immune; behavioural

Stress (both acute and chronic) decreases the resistance of humans and animals to disease. Immune cells have evolved receptors for stress hormones, suggesting that stress-induced changes in immune function provide some benefit. However, these benefits are often unclear, in part because the vertebrate immune system is difficult to study. Our lab examines this question in a simpler insect system. A simpler system is helpful, because answering this question requires experiments spanning multiple levels of analysis (e.g. molecular to behavioural), and an examination of both the physiological mechanisms and their evolutionary significance. As in mammals, insects have a stress hormone (i.e. octopamine). It also depresses disease resistance. In this study, we test whether the stress response selectively depresses immune functions that conflict with it. For example, both the stress and immune responses generate oxidative stress. If both functions were fully activated, the resulting tissue damage may cause even greater declines in survival than stress-induced reductions in disease resistance. I predict that stress hormones reconfigure the immune response so that it relies less on tissue damaging mechanisms. This hypothesis could help explain why stress hormones can both enhance and depress disease resistance. This study has the potential to offer fresh insights into the perennial issue of why stress hormones alter immune function and why chronic stress reduces disease resistance. There are also practical reasons for knowing why stress hormones reduce immunity. It has been suggested that these effects should be blocked by drugs. Without knowing their function, preventing the expression of these ancient conserved responses may bring unintended negative consequences. This study also examines how climate change will alter the impact of chronic stress on disease resistance in insects. I predict that increased temperature will exacerbate the decline in disease resistance caused by chronic stress. Reduced disease resistance in insects will have profound effects on the terrestrial ecosystem and human health (e.g. if it increases the chance that insects will become infected with diseases like West Nile Virus).

压力（急性和慢性）降低了人类和动物对疾病的抵抗力。免疫细胞已经进化出了应激激素的受体，这表明应激诱导的免疫功能变化提供了一些好处。然而，这些好处往往不清楚，部分原因是脊椎动物的免疫系统很难研究。我们的实验室在一个更简单的昆虫系统中研究这个问题。一个更简单的系统很有帮助，因为回答这个问题需要跨越多个层次的分析（例如分子到行为）的实验，以及对生理机制及其进化意义的检查。与哺乳动物一样，昆虫也有一种应激激素（即章鱼胺）。它也会抑制疾病抵抗力。在这项研究中，我们测试了应激反应是否选择性地抑制与之冲突的免疫功能。例如，应激和免疫反应都产生氧化应激。如果这两种功能都被完全激活，所造成的组织损伤可能会导致比压力引起的抗病性下降更大的生存下降。我预测，应激激素重新配置免疫反应，使其更少地依赖于组织损伤机制。这一假说有助于解释为什么应激激素既能增强也能抑制抗病能力。这项研究有可能为长期存在的问题提供新的见解，即为什么应激激素会改变免疫功能，为什么慢性应激会降低疾病抵抗力。还有一些实际的原因可以解释为什么压力荷尔蒙会降低免疫力。有人建议，这些影响应该被药物阻断。在不了解它们的功能的情况下，阻止这些古老的保守反应的表达可能会带来意想不到的负面后果。这项研究还探讨了气候变化将如何改变慢性应激对昆虫抗病性的影响。我预测，温度升高会加剧慢性压力导致的抗病能力下降。昆虫抗病能力的降低将对陆地生态系统和人类健康产生深远的影响（例如，如果它增加了昆虫感染西尼罗河病毒等疾病的机会）。