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

Conor M. Finlay, James E. Parkinson, Lili Zhang, Brian H.k. Chan, Jesuthas Ajendra, Alistair Chenery, Anya Morrison, Irem Kaymak, Emma L. Houlder, Syed Murtuza baker, Ben R. Dickie, Louis Boon, Joanne E. Konkel, Matthew R. Hepworth, Andrew S. Macdonald, Gwendalyn J. Randolph, Dominik Rückerl, Judith E. Allen

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)1064-1081.e10
Number of pages29
JournalImmunity
Volume56
Issue number5
Early online date21 Mar 2023
DOIs
Publication statusPublished - 9 May 2023

Keywords / Materials (for Non-textual outputs)

  • serous cavities
  • helminth
  • litomosoides sigmodontis
  • strain-dependent immunity
  • alternatively activated macrophages
  • filariasis
  • GATA6
  • interleukin 4
  • interleukin 13
  • converting cavity macrophage

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