Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6 ⁺ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206⁺ LYVE1⁺ cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206⁺ macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c⁺CD14⁺CD64⁺ peritoneal cells, which, in turn, resembled human peritoneal CD1c⁺CD14⁻CD64⁻ cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.