Chen Shuxi, Zhang Xinyue, Xiong Zongliang, Khan Asad, Zhou Wendi, Zou Xinyi, Jia Lanlan, Huang Chao, Chen Zhengli, Luo Qihui
Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Chengdu, 611130, China.
Arch Microbiol. 2025 Aug 18;207(9):227. doi: 10.1007/s00203-025-04400-5.
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a pathogenic bacterium that causes acute gastroenteritis. Macrophages play a crucial role in modulating inflammatory responses and eliminating S. Typhimurium infections. In this study, we identified TRIM67, a tripartite motif protein, as a key mediator of macrophage immunity against S. Typhimurium infection. Using S. Typhimurium mouse models, we evaluated the impact of TRIM67 deficiency on liver and spleen inflammation under both normal physiological conditions and S. Typhimurium infection. Mechanistic insights into TRIM67-mediated inflammatory effects were investigated through immunohistochemistry and Western blotting. For in vitro experiments, primary peritoneal macrophages were isolated from Wild-Type(WT) and TRIM67-knockout(KO) mice, and generated TRIM67-overexpressing RAW 264.7 macrophage cell lines. We assessed bacterial load, survival rates, and macrophage-mediated immune responses following S. Typhimurium infection. Our results demonstrated that KO mice exhibited heightened susceptibility to S. Typhimurium infection compared to WT mice. TRIM67 knockout suppressed inflammation in the liver and spleen, impaired monocyte recruitment to infection sites, and reduced macrophage numbers, ultimately leading to increased mortality. Furthermore, TRIM67 knockout inhibited the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, thereby attenuating macrophage immunity and the production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. This study unveils a novel role for TRIM67 in protecting mice against S. Typhimurium infection by regulating inflammation and macrophage survival.
鼠伤寒沙门氏菌（Salmonella enterica serovar Typhimurium，简称鼠伤寒沙门菌）是一种可引发急性肠胃炎的致病细菌。巨噬细胞在调节炎症反应以及消除鼠伤寒沙门菌感染过程中发挥着关键作用。在本研究中，我们鉴定出一种三方基序蛋白TRIM67，它是巨噬细胞抵抗鼠伤寒沙门菌感染免疫反应的关键介质。利用鼠伤寒沙门菌小鼠模型，我们评估了在正常生理条件和鼠伤寒沙门菌感染情况下，TRIM67缺陷对肝脏和脾脏炎症的影响。通过免疫组织化学和蛋白质免疫印迹法对TRIM67介导的炎症效应进行了机制研究。在体外实验中，从野生型（WT）和TRIM67基因敲除（KO）小鼠中分离出原代腹腔巨噬细胞，并构建了过表达TRIM67的RAW 264.7巨噬细胞系。我们评估了鼠伤寒沙门菌感染后的细菌载量、存活率以及巨噬细胞介导的免疫反应。我们的结果表明，与WT小鼠相比，KO小鼠对鼠伤寒沙门菌感染表现出更高的易感性。TRIM67基因敲除抑制了肝脏和脾脏的炎症，损害了单核细胞向感染部位的募集，并减少了巨噬细胞数量，最终导致死亡率增加。此外，TRIM67基因敲除抑制了丝裂原活化蛋白激酶（MAPK）和核因子κB（NF-κB）信号通路的激活，从而削弱了巨噬细胞免疫以及促炎细胞因子（包括TNF-α、IL-1β和IL-6）的产生。本研究揭示了TRIM67在通过调节炎症和巨噬细胞存活来保护小鼠抵抗鼠伤寒沙门菌感染方面的新作用。
