hMDM infection with different bacteria

During an intracellular bacterial infection, the host cell and the infecting pathogen interact through a progressive series of events that may result in many distinct outcomes. To understand the specific strategies our immune system employs to manage attack by diverse pathogens, we sought to identify the unique and the core host and pathogen interactions that occur during infection: We compared in molecular detail the pathways induced across infection by seven diverse bacterial species that constitute many of the main human pathogens: Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Group B Streptococcus, Yersinia pseudotuberculosis, Shigella flexneri and Salmonella enterica. We infected primary human macrophages with each species and used scRNA-Seq to generate a comprehensive dataset of gene expression profiles during bacterial infection. Examining the expression profiles of the infected macrophages across the pathogens, we discovered different modules of infection representing different states through which the infection progresses. The early module captures intra-cellular activity such as lysosome and degranulation, followed by type I IFN signaling, from which results in a cell death module, with a last mode of inflammatory response through response to IL-1. Comparing these modules across the pathogens, we found that their dynamics differ, with some modules active in all species and others which are present in some, but not all pathogens. Our work defines the hallmarks of host-pathogen interactions by identifying recurring properties of infection that can provide insight into diagnostics and therapeutic timing. single cells were infected with diverse bacteria, and harvested after 2 or 4 hors of infection, tagged using cell hashing and processed using 10X scRNA-Seq protocol