Characterization of early stages of in vivo Salmonella infection

During bacteremia, blood-borne bacteria are filtered and cleared by the spleen, the largest lymphoid organ of the body. For this, the spleen is home to several monocyte and macrophage populations that form a vast network of phagocytes competent in identifying and clearing the infectious agent. Intracellular pathogens, such as Salmonella enterica (Sl), have evolved to evade host attack and establish an intracellular niche within macrophages during systemic infection. To date, the specific function of the different monocyte/macrophage populations in orchestrating the response to Sl infection in the spleen is not well described. Here, we characterized the monocyte/macrophage populations at early stages of systemic Sl infection. We found that during the first hours, Sl is restricted by red-pulp macrophages, followed by rapid Sl replication within a yet uncharacterized macrophage population. Using single-cell RNA-seq we suggest the origin of this population from non-classical monocytes, and define unique surface markers, to follow this population in vivo. We propose a model where Sl resides within distinct populations of splenic macrophages at different stages of infection, which determines the cellular infection outcome.