@article{6377fd2684f241a68c7a7030a6d58793,
title = "T helper 2 cells control monocyte to tissue-resident macrophage differentiation during nematode infection of the pleural cavity",
abstract = "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.",
keywords = "serous cavities, helminth, litomosoides sigmodontis, strain-dependent immunity, alternatively activated macrophages, filariasis, GATA6, interleukin 4, interleukin 13, converting cavity macrophage",
author = "Finlay, {Conor M.} and Parkinson, {James E.} and Lili Zhang and Chan, {Brian H.k.} and Jesuthas Ajendra and Alistair Chenery and Anya Morrison and Irem Kaymak and Houlder, {Emma L.} and {Murtuza baker}, Syed and Dickie, {Ben R.} and Louis Boon and Konkel, {Joanne E.} and Hepworth, {Matthew R.} and Macdonald, {Andrew S.} and Randolph, {Gwendalyn J.} and Dominik R{\"u}ckerl and Allen, {Judith E.}",
note = "Funding Information: We thank the exceptional core facilities at the University of Manchester including Flow Cytometry, Biological Service Facility, and Genomics Technology. We thank Qiang Shi for sharing code, Mudassar Iqbal for advice on TFs, Pete Cook for advice on mass cytometry, and Stephen Jenkins and P{\textquoteright}ng Loke for constructive scientific discussion. William Agace, Kara Filbey, and John Grainger provided mouse lines. This work was funded by Medical Research Council-UK ( MR /K01207X/2 ) and Wellcome Trust ( 106898/A/15/Z ) to J.E.A. with additional funding from BBSRC ( BB/T014482/1 ) and a Lister Institute of Preventative Medicine Prize to M.R.H. and NIH R37 AI049653 to G.J.R. Additional diagrams were created using BioRender. Funding Information: We thank the exceptional core facilities at the University of Manchester including Flow Cytometry, Biological Service Facility, and Genomics Technology. We thank Qiang Shi for sharing code, Mudassar Iqbal for advice on TFs, Pete Cook for advice on mass cytometry, and Stephen Jenkins and P'ng Loke for constructive scientific discussion. William Agace, Kara Filbey, and John Grainger provided mouse lines. This work was funded by Medical Research Council-UK (MR/K01207X/2) and Wellcome Trust (106898/A/15/Z) to J.E.A. with additional funding from BBSRC (BB/T014482/1) and a Lister Institute of Preventative Medicine Prize to M.R.H. and NIH R37 AI049653 to G.J.R. Additional diagrams were created using BioRender. C.M.F. and J.E.A. conceptualized and supervised the study and wrote the manuscript. C.M.F. J.E.P. and L.Z. conducted and analyzed most experiments. C.M.F. and J.E.P. conducted computational analysis. D.R. and M.R.H. provided conceptual and technical assistance. B.H.K.C. maintained the parasite lifecycle. J.E.P. B.H.K.C. J.A. A.C. A.M. I.K. and J.E.K. provided technical assistance. B.R.D. performed MRI. L.B. E.L.H. G.J.R. and A.S.M. provided key resources. S.M.B. provided computational assistance. All authors edited and approved the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = may,
day = "9",
doi = "10.1016/j.immuni.2023.02.016",
language = "English",
volume = "56",
pages = "1064--1081.e10",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",
}