Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

Michal Scur; Ahmad Bakur Mahmoud; Sayanti Dey; Farah Abdalbarri; Iona Stylianides; Daniel Medina-Luna; Gayani S. Gamage; Aaron Woblistin; Alexa N.M. Wilson; Haggag S. Zein; Ashley Stueck; Andrew Wight; Oscar A. Aguilar; Francesca Di Cara; Brendon D. Parsons; Mir Munir A. Rahim; James R. Carlyle; Andrew P. Makrigiannis

doi:10.1038/s41467-022-34935-w

Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

Michal Scur, Ahmad Bakur Mahmoud, Sayanti Dey, Farah Abdalbarri, Iona Stylianides, Daniel Medina-Luna, Gayani S. Gamage, Aaron Woblistin, Alexa N.M. Wilson, Haggag S. Zein, Ashley Stueck, Andrew Wight, Oscar A. Aguilar, Francesca Di Cara, Brendon D. Parsons, Mir Munir A. Rahim, James R. Carlyle, Andrew P. Makrigiannis

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13 Citas (Scopus)

Resumen

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b^−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b^−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

Idioma original	English
Número de artículo	7272
Publicación	Nature Communications
Volumen	13
N.º	1
DOI	https://doi.org/10.1038/s41467-022-34935-w
Estado	Published - dic. 2022

Nota bibliográfica

Funding Information:
We acknowledge the support from Dalhousie CORES facilities for flow cytometry and microscopy experiments, as well as the Dalhousie Animal Care facility. The research and M.S. were supported by the Natural Sciences and Engineering Council grant RGPIN/05557-2018 (awarded to A.P.M.). D.M.L. is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. The Clr-b mice were a generous gift from Dr. Matthew T. Gillespie. The anti-NKR-P1B antibody was a generous gift from Dr. Koho Iizuka, University of Minnesota. −/−

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General
General Physics and Astronomy

PubMed: MeSH publication types

Journal Article

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Scur, M., Mahmoud, A. B., Dey, S., Abdalbarri, F., Stylianides, I., Medina-Luna, D., Gamage, G. S., Woblistin, A., Wilson, A. N. M., Zein, H. S., Stueck, A., Wight, A., Aguilar, O. A., Di Cara, F., Parsons, B. D., Rahim, M. M. A., Carlyle, J. R., & Makrigiannis, A. P. (2022). Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death. Nature Communications, 13(1), Artículo 7272. https://doi.org/10.1038/s41467-022-34935-w

Scur, M, Mahmoud, AB, Dey, S, Abdalbarri, F, Stylianides, I, Medina-Luna, D, Gamage, GS, Woblistin, A, Wilson, ANM, Zein, HS, Stueck, A, Wight, A, Aguilar, OA, Di Cara, F , Parsons, BD, Rahim, MMA, Carlyle, JR & Makrigiannis, AP 2022, 'Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death', Nature Communications, vol. 13, n.º 1, 7272. https://doi.org/10.1038/s41467-022-34935-w

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title = "Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death",

abstract = "Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.",

author = "Michal Scur and Mahmoud, {Ahmad Bakur} and Sayanti Dey and Farah Abdalbarri and Iona Stylianides and Daniel Medina-Luna and Gamage, {Gayani S.} and Aaron Woblistin and Wilson, {Alexa N.M.} and Zein, {Haggag S.} and Ashley Stueck and Andrew Wight and Aguilar, {Oscar A.} and {Di Cara}, Francesca and Parsons, {Brendon D.} and Rahim, {Mir Munir A.} and Carlyle, {James R.} and Makrigiannis, {Andrew P.}",

note = "Funding Information: We acknowledge the support from Dalhousie CORES facilities for flow cytometry and microscopy experiments, as well as the Dalhousie Animal Care facility. The research and M.S. were supported by the Natural Sciences and Engineering Council grant RGPIN/05557-2018 (awarded to A.P.M.). D.M.L. is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. The Clr-b mice were a generous gift from Dr. Matthew T. Gillespie. The anti-NKR-P1B antibody was a generous gift from Dr. Koho Iizuka, University of Minnesota. −/− Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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T1 - Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

AU - Scur, Michal

AU - Mahmoud, Ahmad Bakur

AU - Dey, Sayanti

AU - Abdalbarri, Farah

AU - Stylianides, Iona

AU - Medina-Luna, Daniel

AU - Gamage, Gayani S.

AU - Woblistin, Aaron

AU - Wilson, Alexa N.M.

AU - Zein, Haggag S.

AU - Stueck, Ashley

AU - Wight, Andrew

AU - Aguilar, Oscar A.

AU - Di Cara, Francesca

AU - Parsons, Brendon D.

AU - Rahim, Mir Munir A.

AU - Carlyle, James R.

AU - Makrigiannis, Andrew P.

N1 - Funding Information: We acknowledge the support from Dalhousie CORES facilities for flow cytometry and microscopy experiments, as well as the Dalhousie Animal Care facility. The research and M.S. were supported by the Natural Sciences and Engineering Council grant RGPIN/05557-2018 (awarded to A.P.M.). D.M.L. is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. The Clr-b mice were a generous gift from Dr. Matthew T. Gillespie. The anti-NKR-P1B antibody was a generous gift from Dr. Koho Iizuka, University of Minnesota. −/− Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

AB - Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

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Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

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