Unraveling host-pathogen dynamics in a murine Model of septic peritonitis induced by vancomycin-resistant Enterococcus faecium

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

cytokine-mediated signalling pathway; hypothermia; mathematical model; septic peritonitis; vancomycin-resistant Enterococcus faecium.