Immune Response of Drosophila Against Spiroplasma

描述(申请人提供)：了解对病原体的免疫防御机制对于预防和治疗人类传染病非常重要。人类免疫反应的先天分支的重要性越来越被认为是防御许多病原体的关键。无脊椎动物和脊椎动物的先天防御机制表现出惊人的相似性，并且在进化上是保守的。果蝇黑腹果蝇为研究多种微生物病原体的先天反应提供了一种公正而有力的工具。然而，它还没有被用来探索对包括肺炎支原体等人类重要病原体在内的蚊类细菌的先天反应。这项建议的主要目标是利用果蝇(即螺旋体属)自然感染软体动物的优势，发展果蝇作为研究软体动物天然免疫的模式系统。在拟议的研究中，假设自然感染果蝇的软体动物会在果蝇中引发先天免疫反应，这取决于细菌菌株对宿主的表型影响(从轻微到严重)。这些先天反应在无脊椎动物和脊椎动物中很可能是保守的；因此，这项工作将成为研究果蝇先天免疫反应是否有助于开发人类和其他脊椎动物与软糖相关疾病的治疗方法的基础。拟议项目的目的是通过以下具体目标确定果蝇和螺旋体之间相互作用的因素： 目的一、通过血细胞芯片实验确定果蝇体内螺旋体的存在是否会引起血细胞转录组的改变。 目的II.通过蛋白质组学/多肽组学实验，确定果蝇体内螺旋体的存在是否会引起血淋巴蛋白质组的变化。 与公共卫生的相关性拟议的研究将使用果蝇黑腹果蝇来了解有机体对Mollicus纲细菌的天生反应。类中的细菌包括人类的重要病原体，如肺炎支原体。通过了解缺乏适应性免疫系统的果蝇如何与Mollicuts相互作用，我们或许能够理解人类先天反应对防御Mollicuts的贡献。

DESCRIPTION (provided by applicant): Understanding the mechanisms of immune defense against pathogens is important for preventing and treating human infectious diseases. The importance of the innate branch of the human immune response is increasingly recognized as crucial in defense against many pathogens. Innate defense mechanisms of invertebrates and vertebrates show striking similarities and are evolutionary conserved. The fruitfly Drosophila melanogaster has provided an unbiased and powerful tool for examination of innate response against many types of microbial pathogens. However, it has not yet been used to explore innate response against bacteria in the Class Mollicutes, which includes important pathogens of humans such as Mycoplasma pneumoniae. The major goal of this proposal is to develop Drosophila as a model system for studying innate immunity against mollicutes, taking advantage of naturally infecting mollicutes of Drosophila (i.e., genus Spiroplasma). In the proposed study, the hypothesis is that mollicutes that naturally infect Drosophila elicit an innate immune response in the fly, which varies depending on the phenotypic effects (from mild to severe) of the bacterium strain on the host. These innate responses are likely to be conserved across invertebrates and vertebrates; thus, this work will serve as the foundation to study whether Drosophila innate immune response can help develop treatments for mollicute-related illnesses in humans and other vertebrates. The aim of the proposed project is to identify factors involved in the interaction between Drosophila and Spiroplasma via the following Specific Aims: Aim I. Establish whether the presence of Spiroplasma in Drosophila induces changes in the hemocyte transcriptome via hemocyte microarray experiments. Aim II. Establish whether the presence of Spiroplasma in Drosophila induces changes in the hemolymph proteome via proteomics/peptidomics experiments. PUBLIC HEALTH RELEVANCE The proposed research will use the fruitfly Drosophila melanogaster to understand the innate response of organisms against bacteria from the class Mollicutes. Bacteria in the class Mollicutes include important pathogens of humans such as Mycoplasma pneumoniae. By understanding how Drosophila, which lacks an adaptive immune system, interacts with Mollicutes, we may be able to understand the contribution of the human innate response to defense against Mollicutes.