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Nat Immunol. 2019 May;20(5):571-580. doi: 10.1038/s41590-019-0352-y. Epub 2019 Apr 1.

The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation.

Author information

1
Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
2
Laboratory of Myeloid Cell Ontogeny and Functional Specialisation, VIB Center for Inflammation Research, Ghent, Belgium.
3
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
4
Lydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
5
AstraZeneca, Discovery Sciences IMED, Gothenburg, Sweden.
6
Department of Child Health, Division of Clinical and Experimental Sciences, Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, University of Southampton, Southampton, UK.
7
Institute for Life Sciences, University of Southampton, Southampton, UK.
8
National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
9
Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
10
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
11
AstraZeneca RIA IMED, Gothenburg, Sweden.
12
Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. peter.c.cook@manchester.ac.uk.
13
Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. andrew.macdonald@manchester.ac.uk.

Abstract

Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood. We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity. We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner. Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation.

PMID:
30936493
DOI:
10.1038/s41590-019-0352-y
[Indexed for MEDLINE]

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