Data_Sheet_1_TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages.docx

Sepsis is associated with bacterial invasion and inflammation and has a high mortality rate. Previous studies have demonstrated that tripartite motif 59 (TRIM59) was involved in NF-κB signaling and could promote phagocytosis of macrophages, but the role of TRIM59 in sepsis is still unknown. In our study, we found that TRIM59 was downregulated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). In the cecal ligation and puncture (CLP) sepsis mice model, the mortality of Trim59flox/floxLyz-Cre (Trim59-cKO) mice was higher, the immune cell infiltration and damage of liver and lung were more severe, and bacteria burden was increased. We also found that TRIM59 altered the production of pro-inflammation cytokines, as well as macrophage phagocytosis ability. Further analysis indicated that NF-κB signal pathway and Fcγ receptors might be involved in these regulations. Our study demonstrated for the first time that TRIM59 protects mice from sepsis by regulating inflammation and phagocytosis in macrophages.

败血症与细菌侵袭及炎症密切相关，且具有较高的死亡率。既往研究表明，三结构域（TRIM59）参与NF-κB信号传导并能够促进巨噬细胞的吞噬作用，但TRIM59在败血症中的作用尚不明确。在本研究中，我们发现TRIM59在脂多糖（LPS）刺激的骨髓来源的巨噬细胞（BMDMs）中表达下调。在回肠结扎穿孔（CLP）败血症小鼠模型中，Trim59flox/floxLyz-Cre（Trim59-cKO）小鼠的死亡率升高，免疫细胞浸润和肝脏、肺部的损伤更为严重，细菌负荷增加。此外，我们还发现TRIM59改变了促炎细胞因子的产生以及巨噬细胞的吞噬能力。进一步分析表明，NF-κB信号通路和Fcγ受体可能参与这些调节过程。本研究首次证实，TRIM59通过调节巨噬细胞的炎症和吞噬作用，保护小鼠免受败血症的侵袭。