Immune-induction of lipid droplets in Drosophila larval hemocytes

脂滴是细胞质中储存脂肪的细胞器，在脂类中起着基础作用 新陈代谢、能量动态平衡和信号转导。在许多传染病中，它们 积聚在免疫细胞中，可以对机体的能力产生积极或消极的影响 对感染做出反应。尽管取得了重大进展，但很难评估 免疫诱导的机体作为一个整体的LDS。果蝇模特有很好的记录 为先天免疫和LD生物学提供了普遍重要的见解。这个 提出的项目利用果蝇来研究这些领域之间的交叉。 当果蝇幼虫感染细菌时，它们的巨噬细胞样血细胞 (血细胞)迅速积累LDS。细菌细胞壁也可以触发这种反应。 并严重依赖于IMD途径的蛋白质，特别是核因子-kB 转录因子的味道。这是一个非常快速的响应，可以在40秒内检测到LD累积 几分钟的刺激。先天免疫和LD的其他方面的深层保守 苍蝇和哺乳动物之间的生物学表明，这种反应可能具有广泛的重要性。 然而，由于缺乏机械性的理解，目前不可能测试 这一反应的生物学意义。该项目将采用双管齐下的方法来 揭示免疫诱导LD形成的潜在机制。我们将在年确定 哪些组织/细胞NF-kB/AREISH通过组织特异性RNAi驱动LD的形成 接近。也将测试IMD途径的其他组成部分的作用以及 这种反应是否依赖于味精作为转录激活剂的已知功能。至 确定血细胞LD是如何形成的，参与LD生物发生的各种途径以及 营业额将被实验性地操纵，而LD积累的后果 在基础状态和免疫诱导后进行检查。这些研究将产生 用于检验关于功能角色的机械性假设的工具和智力框架 免疫诱导的血细胞LDS，并将照亮一般巨噬细胞的脂质代谢。

Lipid droplets (LDs) are cytoplasmic fat storage organelles with fundamental roles in lipid metabolism, energy homeostasis, and signal transduction. In many infectious diseases, they accumulate in immune cells and can positively or negatively affect the ability of the organism to respond to infection. Despite important advances, it is difficult to assess the relevance of immune-induced LDs for the organism as a whole. Drosophila models have a great track record for providing generally important insights into both innate immunity and LD biology. The proposed project takes advantage of Drosophila to study the intersection between these fields. When Drosophila larvae are infected with bacteria, their macrophage-like blood cells (hemocytes) rapidly accumulate LDs. This response can also be triggered by bacterial cell wall components and depends critically on proteins of the Imd pathway, in particular the NF-kB transcription factor Relish. It is a very rapid response, with LD accumulation detectable within 40 minutes of stimulation. The deep conservation of other aspects of innate immunity and LD biology between flies and mammals suggests that this response could be broadly important. However, because a mechanistic understanding is lacking, it is currently impossible to test the biological significance of the response. This project will employ a two-pronged approach to uncover the underlying mechanisms of immune-induced LD formation. We will determine in which tissues/cells NF-kB/Relish functions to drive LD formation, with a tissue-specific RNAi approach. The role of other components of the Imd pathway will also be tested as well as whether the response relies on the known function of Relish as a transcriptional activator. To determine how the hemocyte LDs form, various pathways involved in LD biogenesis and turnover will be manipulated experimentally and the consequences for LD accumulation examined, both in the basal state and after immune induction. These studies will generate the tools and intellectual framework to test mechanistic hypotheses about the functional role of immune-induced hemocyte LDs and will illuminate macrophage lipid metabolism in general.