Abstract
Heterogeneity in host-pathogen interaction includes bacterial and host cell diversity, which together can lead to different infection outcomes. We report on macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. We found a highly inflammatory state which included four conserved transcriptional programs – response to stimulus, activation of immune response, antigen presentation, and T cell activation – induced sequentially and punctuated by a ‘mid-infection transition’ between bacterial sensing and signaling. We validated these modules and their dynamic relationship in an in vivo mouse model of infection. Analysis of stimulation with 6 additional species – Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri and Salmonella enterica – reveals conservation of this program with distinct rates of module expression between species. Our work defines the hallmarks of host-pathogen interactions by identifying recurring properties of infection, providing insights into clinical diagnostics and therapeutic timing.
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