Proliferation is a driver of quorum sensing in an in vitro model of tissue resident macrophages

Macrophages coordinate the initial host inflammatory response to tissue infection as well as mediating the reparative phase by producing growth factors that promote tissue repair. One model of this functional dichotomy is that peripherally recruited monocyte-derived macrophages drive acute inflammatory responses to infection, whereas tissue resident macrophages are responsible for tissue repair. Alternatively, inflammation and repair may be inter-dependent molecular programs, such that both recruited and resident cells have equivalent capacity to contribute. In this study, induced pluripotent stem cells or peripheral blood monocytes were used to generate models of tissue-resident and recruited macrophages, respectively. Using single-cell sequencing, we assessed whether lipopolysaccharide activation drives heterogeneous responses in these two macrophage models. We observe heterogeneity at population and gene expression level in the activation programs adopted by either macrophage population. We further identify proliferation to be a driver of quorum sensing in LPS responsiveness. Our findings highlight the usefulness of this model system to explore the differences between recruited and resident macrophages in response to tissue infection.