%0 Journal Article
%T Unraveling host-pathogen dynamics in a murine Model of septic peritonitis induced by vancomycin-resistant Enterococcus faecium.
%A Yuan X
%A Song X
%A Zhang X
%A Hu L
%A Zhou D
%A Zhang J
%A Dai C
%J Virulence
%V 15
%N 1
%D 2024 Dec
%M 38951957
%F 5.428
%R 10.1080/21505594.2024.2367659
%X 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.