Host-Pathogen Interactions as a Resource-Competition Problem

宿主-病原体相互作用作为资源竞争问题

• 批准号: BB/I02249X/1
• 负责人: Kenneth Wilson
• 金额: $ 58.36万
• 依托单位: Lancaster University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI02249X%2F1
• 关键词: Host; Pathogen; Interactions; Resource; Competition

Malnutrition and obesity are two of the most prevalent nutritional conditions affecting humans around the world today. As well as their obvious pathological effects on body condition and general well-being, sufferers may also have a reduced capacity to resist infections. In light of this, there has been a growth in the use of nutritional supplements aimed at boosting immunity, practiced both by the medical establishment (e.g. iron and vitamin supplements) and on the medical fringes. Whilst there is little doubt that certain key nutrients can play an important role in fighting infections, many of the studies to date have been conducted on single nutrients in isolation, without considering how they interact with other components of the diet, and without a robust framework for assessing their efficacy or mechanisms of action. The aim of the current proposal is to combine the theories provided by nutritional biology, ecological immunology and community ecology to develop a new framework that will allow us to test ideas about the importance of nutrition in determining the outcome of infections. Insects and their pathogens can provide useful models for understanding human diseases. This is because the insect's relatively simple immune system shows striking parallels with the human innate immune system. Moreover, insects are often easier to work with than humans, yet exhibit many of the same nutritional behaviours, such as obesity, anorexia and self-medication. We will use the caterpillar, Spodoptera littoralis, and the bacterium, Bacillus subtilis, as a model system for exploring the effects of macronutrients on innate immunity and pathogen resistance. Our previous studies have shown that healthy insects perform best on a diet that is roughly balanced in terms the relative amounts of protein (P) and carbohydrate (C), the two most important macronutrients for insects. If the insect eats too much or too little P or C, then it performs less well, indicating that this is the 'optimal' diet when uninfected. In contrast, insects that have been infected with pathogens, like B. subtilis, have much higher survival rates if they eat a diet extremely rich in protein. Moreover, if they are given a choice, infected insects will feed on a diet with a high protein content to aid their survival. We will use a step-wise experimental approach to determine whether we can predict the outcome of pathogen infections by understanding how the host and pathogen fare when grown in isolation. In particular, we will test the null hypothesis that the outcome of the infection (e.g. whether the insect lives or dies) is determined solely by the nutritional requirements of the host and pathogen. We will use 20 different artificial diets that vary in their P:C composition, so that we force the insects to ingest different amounts of P and C. 1. We will start by establishing how the diet of the insect affects the nutritional composition of its blood, which is where the bacteria will feed. 2. We will then grow the bacteria in a range of broths that have the same nutritional composition as the insect blood on each diet, but without blood cells and other immune defences. This will show us the nutritional requirements of the bacterium in the absence of the host. 3. We will then determine how the insect host's immune defences perform in the absence of the pathogen by injecting the insect with dead bacteria to stimulate the immune response, which we will be quantified using genetic and other methods. These first three experiments will allow us to determine how the performance of the host (insect) and pathogen (bacteria) differs on different diets and to make predictions about winners and losers based on assumptions about who controls nutrient use. 4. Finally, we will inject caterpillars with live bacteria and quantify the outcome in terms of bacterial growth rates and insect growth/survival, allowing us to test these predictions.

营养不良和肥胖是当今影响世界各地人类的两种最普遍的营养状况。除了对身体状况和总体健康有明显的病理影响外，患者抵抗感染的能力也可能降低。有鉴于此，旨在提高免疫力的营养补充剂的使用有所增加，医疗机构(如铁和维生素补充剂)和医疗边缘人都在使用这种补充剂。虽然某些关键营养素在抵抗感染方面可以发挥重要作用，这一点毋庸置疑，但到目前为止，许多研究都是孤立地对单一营养素进行的，没有考虑它们如何与饮食中的其他成分相互作用，也没有一个强有力的框架来评估它们的有效性或作用机制。目前这项提议的目的是将营养生物学、生态免疫学和社区生态学提供的理论结合起来，开发一个新的框架，使我们能够测试关于营养在决定感染结果方面的重要性的想法。昆虫及其病原体可以为理解人类疾病提供有用的模型。这是因为这种昆虫相对简单的免疫系统与人类的先天免疫系统有着惊人的相似之处。此外，昆虫通常比人类更容易接触，但表现出许多相同的营养行为，如肥胖、厌食症和自我药物治疗。我们将使用毛虫、斜纹夜蛾和枯草杆菌作为模式系统，探索大量营养素对天然免疫和病原菌抵抗力的影响。我们之前的研究表明，健康的昆虫在蛋白质(P)和碳水化合物(C)的相对含量大致平衡的饮食中表现最好，这是昆虫最重要的两种常量营养素。如果昆虫吃太多或太少的磷或碳，那么它的表现就不太好，这表明这是未感染时的最佳饮食。相比之下，被病原体感染的昆虫，如枯草杆菌，如果吃蛋白质含量极高的食物，存活率要高得多。此外，如果让它们选择，受感染的昆虫将以高蛋白含量的食物为食，以帮助它们生存。我们将使用循序渐进的实验方法来确定我们是否可以通过了解宿主和病原体在隔离生长时的表现来预测病原体感染的结果。特别是，我们将检验零假设，即感染的结果(例如昆虫的生存或死亡)完全由宿主和病原体的营养需求决定。我们将使用20种不同的人工饲料，它们的P：C组成各不相同，因此我们迫使昆虫摄入不同数量的P和C。我们将首先确定昆虫的饮食如何影响其血液的营养成分，细菌将在血液中觅食。2.然后，我们将在一系列肉汤中培养细菌，这些肉汤的营养成分与每种饮食中的昆虫血液相同，但没有血细胞和其他免疫防御系统。这将向我们展示在没有宿主的情况下细菌的营养需求。3.然后，我们将通过向昆虫注射死菌来刺激免疫反应，从而确定昆虫宿主在没有病原体的情况下的免疫防御表现，我们将使用遗传和其他方法进行量化。这前三个实验将使我们能够确定寄主(昆虫)和病原体(细菌)在不同饮食中的表现如何不同，并根据谁控制营养使用的假设来预测赢家和输家。4.最后，我们将给毛虫注射活细菌，并根据细菌生长速度和昆虫生长/存活来量化结果，使我们能够检验这些预测。

项目成果

Dynamics of macronutrient self-medication and illness-induced anorexia in virally infected insects.

• DOI: 10.1111/1365-2656.12127
• 发表时间: 2014-01
• 期刊: The Journal of animal ecology
• 作者: Povey S;Cotter SC;Simpson SJ;Wilson K
• 通讯作者: Wilson K

Behavioral Microbiomics: A Multi-Dimensional Approach to Microbial Influence on Behavior.

• DOI: 10.3389/fmicb.2015.01359
• 发表时间: 2015
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Wong AC;Holmes A;Ponton F;Lihoreau M;Wilson K;Raubenheimer D;Simpson SJ
• 通讯作者: Simpson SJ

Osmolality as a Novel Mechanism Explaining Diet Effects on the Outcome of Infection with a Blood Parasite.

渗透压作为一种新机制解释饮食对血液寄生虫感染结果的影响。

• DOI: 10.1016/j.cub.2020.04.058
• 发表时间: 2020
• 期刊: CB
• 作者: Wilson K

Macronutrients modulate survival to infection and immunity in Drosophila

• DOI: 10.1111/1365-2656.13126
• 发表时间: 2020-02-01
• 期刊: JOURNAL OF ANIMAL ECOLOGY
• 影响因子: 4.8
• 作者: Ponton, Fleur;Morimoto, Juliano;Simpson, Stephen J.
• 通讯作者: Simpson, Stephen J.

A comparison of the TC10 automated cell counter and the hemocytometer for quantifying insect hemocytes

TC10 自动细胞计数器和血细胞计数仪用于昆虫血细胞定量的比较

• 期刊: Cell Counting
• 作者: Joanna Randall (Author)