当前位置: X-MOL 学术EMBO J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to bacterial infection
The EMBO Journal ( IF 11.4 ) Pub Date : 2022-10-25 , DOI: 10.15252/embj.2021108970
Orsolya Bilkei-Gorzo 1, 2 , Tiaan Heunis 3 , José Luis Marín-Rubio 3 , Francesca Romana Cianfanelli 3 , Benjamin Bernard Armando Raymond 3 , Joseph Inns 3 , Daniela Fabrikova 1 , Julien Peltier 2, 3 , Fiona Oakley 3, 4 , Ralf Schmid 5, 6 , Anetta Härtlova 1, 2, 3 , Matthias Trost 2, 3
Affiliation  

Phagocytosis is a key process in innate immunity and homeostasis. After particle uptake, newly formed phagosomes mature by acquisition of endolysosomal enzymes. Macrophage activation by interferon gamma (IFN-γ) increases microbicidal activity, but delays phagosomal maturation by an unknown mechanism. Using quantitative proteomics, we show that phagosomal proteins harbour high levels of typical and atypical ubiquitin chain types. Moreover, phagosomal ubiquitylation of vesicle trafficking proteins is substantially enhanced upon IFN-γ activation of macrophages, suggesting a role in regulating phagosomal functions. We identified the E3 ubiquitin ligase RNF115, which is enriched on phagosomes of IFN-γ activated macrophages, as an important regulator of phagosomal maturation. Loss of RNF115 protein or ligase activity enhanced phagosomal maturation and increased cytokine responses to bacterial infection, suggesting that both innate immune signalling from the phagosome and phagolysosomal trafficking are controlled through ubiquitylation. RNF115 knock-out mice show less tissue damage in response to S. aureus infection, indicating a role of RNF115 in inflammatory responses in vivo. In conclusion, RNF115 and phagosomal ubiquitylation are important regulators of innate immune functions during bacterial infections.

中文翻译:

E3 泛素连接酶 RNF115 调节吞噬体成熟和宿主对细菌感染的反应

吞噬作用是先天免疫和体内平衡的关键过程。颗粒摄取后,新形成的吞噬体通过获得内溶酶体酶而成熟。干扰素γ (IFN-γ) 激活巨噬细胞会增加杀菌活性,但会通过未知机制延迟吞噬体成熟。使用定量蛋白质组学,我们表明吞噬体蛋白具有高水平的典型和非典型泛素链类型。此外,巨噬细胞的 IFN-γ 激活后,囊泡运输蛋白的吞噬体泛素化显着增强,表明其在调节吞噬体功能中发挥作用。我们发现 E3 泛素连接酶 RNF115 富集在 IFN-γ 激活的巨噬细胞的吞噬体上,是吞噬体成熟的重要调节因子。RNF115蛋白或连接酶活性的丧失增强了吞噬体的成熟并增加了细胞因子对细菌感染的反应,这表明来自吞噬体的先天免疫信号和吞噬溶酶体的运输都是通过泛素化来控制的。RNF115 敲除小鼠表现出较少的组织损伤金黄色葡萄球菌感染,表明 RNF115 在体内炎症反应中的作用。总之,RNF115 和吞噬体泛素化是细菌感染期间先天免疫功能的重要调节因子。
更新日期:2022-10-25
down
wechat
bug