Single-cell analysis of CX3CR1⁺ cells reveal a pathogenic role for BIRC5⁺ myeloid proliferating cells driven by Staphylococcus aureus leukotoxins

Abstract

Our previous studies identified a population of stem cell-like proliferating myeloid cells within inflamed tissues that could serve as a reservoir for tissue macrophages to adopt different activation states depending on the microenvironment. By lineage tracing cells derived from CX3CR1⁺ precursors in mice during infection and profiling by scRNA-seq, here we identify a cluster of BIRC5⁺ myeloid cells that expanded in the liver during either chronic infection with the parasite Schistosoma mansoni or the bacterial pathogen Staphylococcus aureus. In the absence of tissue damaging toxins, S. aureus infection does not elicit these BIRC5⁺ cells. Moreover, deletion of BIRC5 from CX3CR1 expressing cells results in improved survival during S. aureus infection. Hence, the combination of scRNA-Seq and genetic fate mapping CX3CR1⁺ cells revealed a toxin dependent pathogenic role for BIRC5 in myeloid cells during S. aureus infection.