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A systems biology analysis of the Drosophila phagosome

机译：果蝇吞噬体的系统生物学分析。

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Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence(1,2). During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated(3). Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite the crucial role of phagosomes in immunity, their components and organization are not fully defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from the genetically tractable model organism Drosophila melanogaster and address the complex dynamic interactions between proteins within this organelle and their involvement in particle engulfment. Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these were organized by protein - protein interactions to generate the 'phagosome interactome', a detailed protein - protein interaction network of this subcellular compartment. These networks predicted both the architecture of the phagosome and putative biomodules. The contribution of each protein and complex to bacterial internalization was tested by RNA-mediated interference and identified known components of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis such as the 'exocyst'(4), a macromolecular complex required for exocytosis but not previously implicated in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power of applying this approach to the study of complex cellular processes and organelles and expect that this detailed model of the phagosome will provide a new framework for studying host pathogen interactions and innate immunity.
机译：吞噬细胞在胚胎发生过程中对组织重塑起关键作用，此后是免疫防御的主要效应器（1,2）。在吞噬过程中，颗粒被内化为“吞噬体”，即细胞器，从中开始免疫过程，如微生物破坏和抗原提呈（3）。某些病原体已经进化出逃避免疫系统并在吞噬细胞中未被发现的机制，因此很明显，对该过程的详细了解对于理解先天和适应性免疫的许多方面至关重要。然而，尽管吞噬体在免疫中起着至关重要的作用，但它们的组成和组织仍未完全确定。在这里，我们对从遗传易处理的模式生物果蝇（Drosophila melanogaster）衍生的细胞中分离的吞噬体进行系统生物学分析，并研究该细胞器内蛋白质之间的复杂动态相互作用及其与粒子吞噬的关系。蛋白质组学分析鉴定出617种可能与果蝇吞噬体相关的蛋白质。这些通过蛋白质-蛋白质相互作用来组织，以产生“吞噬体相互作用组”，即该亚细胞区室的详细的蛋白质-蛋白质相互作用网络。这些网络预测了吞噬体和推定的生物模块的体系结构。通过RNA介导的干扰测试了每种蛋白质和复合物对细菌内在化的贡献，并确定了吞噬机制的已知成分。此外，对吞噬作用调节剂的预测和验证，例如“胞囊”（4），是胞吞作用所需的大分子复合物，但以前并未参与吞噬作用，从而验证了这一策略。在生成这种“基于系统的模型”时，我们展示了将这种方法应用于复杂细胞过程和细胞器研究的力量，并期望这种吞噬体的详细模型将为研究宿主病原体相互作用和先天免疫力提供新的框架。

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