Unraveling host-pathogen dynamics in a murine model of septic peritonitis induced by vancomycin-resistant <i>Enterococcus faecium</i>

Vancomycin-resistant <i>Enterococcus faecium</i> (<i>E. faecium</i>) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing <i>E. faecium</i>, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and <i>E. faecium</i> 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 <i>E. faecium</i> triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.

耐万古霉素屎肠球菌（Vancomycin-resistant Enterococcus faecium，简称E. faecium）感染与更高的死亡率相关。既往研究已强调天然免疫细胞及信号通路在清除E. faecium中的重要性，但目前仍缺乏针对宿主-病原体互作的系统性分析。本研究利用脓毒性腹膜炎小鼠模型，探究了宿主与E. faecium之间的互作关系。在给予亚致死剂量菌液后，我们观察到小鼠脓毒症评分与组织学评分显著升高，体重、细菌负荷、中性粒细胞与巨噬细胞浸润量均出现下降，同时细胞因子介导的信号通路被全面激活。在接受致死剂量菌液的小鼠中，与正常体温组相比，低体温处理可显著改善小鼠生存率，降低细菌负荷、细胞因子水平以及MHC-II⁺招募巨噬细胞的CD86表达。本研究通过80只动物的观测数据构建了数学模型，该模型可复现宿主-病原体互作过程，并进一步验证了低体温的治疗获益。上述研究结果表明，E. faecium可触发细胞因子介导的信号通路的过度激活，而低体温可通过降低细菌负荷与炎症反应改善疾病预后。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于耐万古霉素粪肠球菌引起的小鼠败血症腹膜炎模型，通过实验数据揭示了宿主-病原体相互作用机制。研究发现亚致死剂量感染会全面激活细胞因子信号通路，而低温治疗在致死剂量下能改善生存率、减少细菌负荷和炎症反应。数据集还包括基于80只动物观察数据构建的数学模型，进一步验证了低温治疗的益处，为相关感染疾病研究提供了重要实验和理论支持。