The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation
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.
Immunology, macrophage, Inflammation, il-4
571-580
Svedberg, Freya R.
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Brown, Sheila L.
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Krauss, Maria Z.
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Campbell, Laura
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Sharpe, Catherine
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Clausen, Maryam
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Howell, Gareth J.
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Clark, Howard
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Madsen, Jens
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Evans, Christopher M.
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Sutherland, Tara E.
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Ivens, Alasdair C.
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Thornton, David J.
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Grencis, Richard K.
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Hussell, Tracy
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Cunoosamy, Danen M.
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Cook, Peter C.
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MacDonald, Andrew S.
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1 April 2019
Svedberg, Freya R.
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Brown, Sheila L.
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Krauss, Maria Z.
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Campbell, Laura
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Sharpe, Catherine
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Clausen, Maryam
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Howell, Gareth J.
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Clark, Howard
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Madsen, Jens
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Evans, Christopher M.
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Sutherland, Tara E.
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Ivens, Alasdair C.
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Thornton, David J.
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Grencis, Richard K.
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Hussell, Tracy
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Cunoosamy, Danen M.
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Cook, Peter C.
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MacDonald, Andrew S.
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Svedberg, Freya R., Brown, Sheila L., Krauss, Maria Z., Campbell, Laura, Sharpe, Catherine, Clausen, Maryam, Howell, Gareth J., Clark, Howard, Madsen, Jens, Evans, Christopher M., Sutherland, Tara E., Ivens, Alasdair C., Thornton, David J., Grencis, Richard K., Hussell, Tracy, Cunoosamy, Danen M., Cook, Peter C. and MacDonald, Andrew S.
(2019)
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation.
Nature Immunology, 20, .
(doi:10.1038/s41590-019-0352-y).
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.
Text
Cook et al 2018_merged_final
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Accepted/In Press date: 14 February 2019
Published date: 1 April 2019
Keywords:
Immunology, macrophage, Inflammation, il-4
Identifiers
Local EPrints ID: 430653
URI: http://eprints.soton.ac.uk/id/eprint/430653
ISSN: 1529-2908
PURE UUID: 308577f9-3110-4061-9a0a-9bbc5ed080c3
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Date deposited: 07 May 2019 16:30
Last modified: 16 Mar 2024 07:44
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Contributors
Author:
Freya R. Svedberg
Author:
Sheila L. Brown
Author:
Maria Z. Krauss
Author:
Laura Campbell
Author:
Catherine Sharpe
Author:
Maryam Clausen
Author:
Gareth J. Howell
Author:
Howard Clark
Author:
Jens Madsen
Author:
Christopher M. Evans
Author:
Tara E. Sutherland
Author:
Alasdair C. Ivens
Author:
David J. Thornton
Author:
Richard K. Grencis
Author:
Tracy Hussell
Author:
Danen M. Cunoosamy
Author:
Peter C. Cook
Author:
Andrew S. MacDonald
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