T helper 2 cells control monocyte to tissue-resident macrophage differentiation during nematode infection of the pleural cavity

The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies per-formed in C57BL/6 mice. Here, using both C57BL/6 and BALB/c mice, we analyze immune cells in the pleural cavity. Unlike C57BL/6 mice, naive tissue-resident large-cavity macrophages (LCMs) of BALB/c mice failed to fully implement the tissue-residency program. Following infection with a pleural-dwelling nematode, these pre-existing differences were accentuated with LCM expansion occurring in C57BL/6, but not in BALB/c mice. While infection drove monocyte recruitment in both strains, only in C57BL/6 mice were monocytes able to efficiently integrate into the resident pool. Monocyte-to-macrophage conversion required both T cells and interleukin-4 receptor alpha (IL-4Ra) signaling. The transition to tissue residency altered macro-phage function, and GATA6(+) tissue-resident macrophages were required for host resistance to nematode infection. Therefore, during tissue nematode infection, T helper 2 (Th2) cells control the differentiation pathway of resident macrophages, which determines infection outcome.

Automated summary

The recent revolution in tissue-resident macrophage biology has largely relied on studies performed in C57BL/6 mice. In this study, using both C57BL/6 and BALB/c mice, researchers analyzed immune cells in the pleural cavity. They found that the tissue-resident macrophages of BALB/c mice failed to fully implement the tissue-residency program compared to C57BL/6 mice. Infection with a pleural-dwelling nematode further accentuated these differences, with only C57BL/6 mice showing expansion of tissue-resident macrophages.