Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of C. elegans with P. aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal PI(4,5)P2 and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity, and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.

中文翻译：

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磷脂酰肌醇 4,5-二磷酸的内体分解代谢对于增强抵抗病原体的能力至关重要。


内体的特征是存在各种磷酸肌醇，这些磷酸肌醇对于定义膜特性至关重要。然而，内体磷酸肌醇代谢与先天免疫之间的相互作用尚未完全了解。在这里，我们的研究结果强调了 RAB-10/Rab10 参与调节先天免疫的进化连续性。线虫感染铜绿假单胞菌后，在肠道中观察到 RAB-10 活性增加。相反，当RAB-10缺失时，肠道二酰甘油（DAG）减少，动物对病原体的反应受损。进一步的研究表明，UNC-16/JIP3 作为 RAB-10 效应子，促进磷脂酶 EGL-8 募集到内体。这导致内体 PI(4,5)P2 减少和 DAG 升高，以及 PMK-1/p38 MAPK 先天免疫途径的激活。值得注意的是，UNC-16 的二聚化是其与 RAB-10(GTP) 相互作用和招募 EGL-8 的先决条件。此外，我们确定，感染引起的 RAB-10 活性升高是由于 LET-413/Erbin 表达增加，并且确定核受体 NHR-25/NR5A1/2 对于这种增加是必不可少的。因此，本研究阐明了内体 PI(4,5)P2 分解代谢在增强先天免疫中的重要性，并概述了 NHR-25 介导的肠上皮病原体检测机制。