Immune Response of Drosophila Against Spiroplasma

描述（由申请人提供）：了解免疫防御病原体的机制对预防和治疗人类传染病很重要。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，并具有进化保守性。果蝇黑腹果蝇已经提供了一个公正和强大的工具来检查先天反应对许多类型的微生物病原体。然而，它还没有被用于探索对Mollicutes类细菌的先天反应，其中包括重要的人类病原体，如肺炎支原体。本课题的主要目标是利用果蝇（即螺旋体属）自然感染的毛菌，将果蝇发展为研究针对毛菌的先天免疫的模型系统。在提出的研究中，假设是自然感染果蝇的分子在果蝇中引起先天免疫反应，这种反应取决于细菌菌株对宿主的表型效应（从轻微到严重）。这些先天反应可能在无脊椎动物和脊椎动物中都是保守的；因此，这项工作将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分子相关疾病的治疗方法奠定基础。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相关因素：

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.