biostudies-literatureFinlay CMNIAID NIH HHSMedical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Council1064-1081.e10https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616141biostudies-literatureUnknown56(5)The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed 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-4Rα) signaling. The transition to tissue residency altered macrophage 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.ImmunityT helper 2 cells control monocyte to tissue-resident macrophage differentiation during nematode infection of the pleural cavity.PMC7616141MR/K01207X/1106898/A/15/ZMR/W018748/1MR/K01207X/2106898BB/T014482/1R37 AI049653Konkel JEKaymak IRuckerl DRandolph GJFinlay CMBoon LMorrison AZhang LAllen JEChan BHKChenery AMacDonald ASHoulder ELAjendra JParkinson JEDickie BRHepworth MRMurtuza Baker SfalseT 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 performed 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-4Rα) signaling. The transition to tissue residency altered macrophage 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.2023-01-01T00:00:00Z2023 May2026-06-02T22:12:21.018Z2024-10-18T19:32:14.789ZS-EPMC76161413694819310.1016/j.immuni.2023.02.016