School of Life Sciences, Ludong University, Yantai, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Virulence. 2024 Dec;15(1):2367659. doi: 10.1080/21505594.2024.2367659. Epub 2024 Jul 1.
Vancomycin-resistant () infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing , but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.
耐万古霉素肠球菌()感染与更高的死亡率相关。既往研究强调固有免疫细胞和信号通路在清除中的重要性,但宿主-病原体相互作用的综合分析尚缺乏。在这里,我们在脓毒性腹膜炎的小鼠模型中研究了宿主和的相互作用。在注射亚致死剂量后,我们观察到小鼠脓毒症评分和组织学评分显著升高,体重和细菌负荷降低,中性粒细胞和巨噬细胞浸润,以及细胞因子介导的信号通路全面激活。在接受致死剂量的小鼠中,与常温组相比,低温显著提高了生存率,降低了细菌负荷、细胞因子和 MHC-II 募集的巨噬细胞上的 CD86 表达。通过对 80 只动物的观测数据构建的数学模型,再现了宿主-病原体的相互作用,并进一步验证了低温的益处。这些发现表明,触发了严重的细胞因子介导的信号通路激活,而低温可以通过降低细菌负荷和炎症来改善预后。