Downregulation of Perilipin1 by the Immune Deficiency Pathway Leads to Lipid Droplet Reconfiguration and Adaptation to Bacterial Infection in Drosophila
Downregulation of Perilipin1 by the Immune Deficiency Pathway Leads to Lipid Droplet Reconfiguration and Adaptation to Bacterial Infection in Drosophila
复制标题
免疫缺陷途径对 Perilipin1 的下调导致果蝇脂滴重构和对细菌感染的适应。
DOI：
10.4049/jimmunol.2100343
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发表时间：
2021-11-01
影响因子：
4.4
通讯作者：
Pan, Lei
中科院分区：
文献类型：
--
作者：
Wang, Lei;Lin, Jiaxin;Pan, Lei
脂滴（LD）是高度动态的细胞内细胞器，对于脂质代谢至关重要。然而，在对细菌感染的先天免疫反应过程中，LD 的结构和功能的动态变化及其潜在机制仍然很大程度上未知。在这项研究中，我们追踪了短暂细菌感染后果蝇脂肪体中 LD 的时程形态。详细分析表明，参与 LD 调节的核心基因 perilipin1 (plin1) 受到免疫缺陷信号传导的抑制，而免疫缺陷信号传导是果蝇的一种主要先天免疫途径。在免疫激活过程中，下调的 plin1 会促进 LD 的增大，从而减轻免疫反应相关的活性氧应激。因此，LDs 的生长可能是响应免疫缺陷激活而维持氧化还原稳态的主动适应。因此，我们的研究提供了证据，表明 plin1 作为 LD 重构的调节剂，调节感染诱导的发病机制，并且 plin1 可能是协调炎症消退和脂质代谢的潜在治疗靶点
Lipid droplets (LDs), the highly dynamic intracellular organelles, are critical for lipid metabolism. Dynamic alterations in the configurations and functions of LDs during innate immune responses to bacterial infections and the underlying mechanisms, however, remain largely unknown. In this study, we trace the time-course morphology of LDs in fat bodies of Drosophila after transient bacterial infection. Detailed analysis shows that perilipin1 (plin1), a core gene involved in the regulation of LDs, suppressed by the immune deficiency signaling, one major innate immune pathway in Drosophila. During immune activation, downregulated plin1 promotes the enlargement of LDs, which in turn alleviates immune reaction -associated reactive oxygen species stress. Thus, the growth of LDs is likely an active adaptation to maintain redox homeostasis in response to immune deficiency activation. Therefore, our study provides evidence that plin1 serves as a modulator on LDs' reconfiguration regulating infection-induced pathogenesis, and plin1 might be a potential therapeutic target for coordinating inflammation resolution and lipid metabolism