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mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis

Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrog...

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Autores principales: Hallowell, R. W., Collins, S. L., Craig, J. M., Zhang, Y., Oh, M., Illei, P. B., Chan-Li, Y., Vigeland, C. L., Mitzner, W., Scott, A. L., Powell, J. D., Horton, M. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290163/
https://www.ncbi.nlm.nih.gov/pubmed/28128208
http://dx.doi.org/10.1038/ncomms14208
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author Hallowell, R. W.
Collins, S. L.
Craig, J. M.
Zhang, Y.
Oh, M.
Illei, P. B.
Chan-Li, Y.
Vigeland, C. L.
Mitzner, W.
Scott, A. L.
Powell, J. D.
Horton, M. R.
author_facet Hallowell, R. W.
Collins, S. L.
Craig, J. M.
Zhang, Y.
Oh, M.
Illei, P. B.
Chan-Li, Y.
Vigeland, C. L.
Mitzner, W.
Scott, A. L.
Powell, J. D.
Horton, M. R.
author_sort Hallowell, R. W.
collection PubMed
description Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.
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spelling pubmed-52901632017-02-07 mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis Hallowell, R. W. Collins, S. L. Craig, J. M. Zhang, Y. Oh, M. Illei, P. B. Chan-Li, Y. Vigeland, C. L. Mitzner, W. Scott, A. L. Powell, J. D. Horton, M. R. Nat Commun Article Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses. Nature Publishing Group 2017-01-27 /pmc/articles/PMC5290163/ /pubmed/28128208 http://dx.doi.org/10.1038/ncomms14208 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Hallowell, R. W.
Collins, S. L.
Craig, J. M.
Zhang, Y.
Oh, M.
Illei, P. B.
Chan-Li, Y.
Vigeland, C. L.
Mitzner, W.
Scott, A. L.
Powell, J. D.
Horton, M. R.
mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
title mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
title_full mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
title_fullStr mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
title_full_unstemmed mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
title_short mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
title_sort mtorc2 signalling regulates m2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290163/
https://www.ncbi.nlm.nih.gov/pubmed/28128208
http://dx.doi.org/10.1038/ncomms14208
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