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  Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages

Huang, S.-C.-C., Everts, B., Ivanova, Y., O'Sullivan, D., Nascimento, M., Smith, A. M., et al. (2014). Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nature Immunology, 15, 846-855. doi:10.1038/ni.2956.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0006-614B-9 Version Permalink: https://hdl.handle.net/21.11116/0000-0006-628C-E
Genre: Journal Article

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 Creators:
Huang, Stanley Ching-Cheng1, Author
Everts, Bart1, Author
Ivanova, Yulia1, Author
O'Sullivan, David2, Author           
Nascimento, Marcia1, Author
Smith, Amber M1, Author
Beatty, Wandy1, Author
Love-Gregory, Latisha1, Author
Lam, Wing Y1, Author
O'Neill, Christina M1, Author
Yan, Cong1, Author
Du, Hong1, Author
Abumrad, Nada A1, Author
Urban, Joseph F Jr1, Author
Artyomov, Maxim N1, Author
Pearce, Edward J.2, Author           
Pearce, Erika L.2, Author           
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1External Organizations, ou_persistent22              
2Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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 Abstract: Alternative (M2) activation of macrophages driven via the α-chain of the receptor for interleukin 4 (IL-4Rα) is important for immunity to parasites, wound healing, the prevention of atherosclerosis and metabolic homeostasis. M2 polarization is dependent on fatty acid oxidation (FAO), but the source of the fatty acids that support this metabolic program has not been clear. We found that the uptake of triacylglycerol substrates via the scavenger receptor CD36 and their subsequent lipolysis by lysosomal acid lipase (LAL) was important for the engagement of elevated oxidative phosphorylation, enhanced spare respiratory capacity (SRC), prolonged survival and expression of genes that together define M2 activation. Inhibition of lipolysis suppressed M2 activation during infection with a parasitic helminth and blocked protective responses to this pathogen. Our findings delineate a critical role for cell-intrinsic lysosomal lipolysis in M2 activation.

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Language(s): eng - English
 Dates: 2014-09
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/ni.2956
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Title: Nature Immunology
  Other : Nat. Immunol.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: 15 Sequence Number: - Start / End Page: 846 - 855 Identifier: ISSN: 1529-2908
CoNE: https://pure.mpg.de/cone/journals/resource/974392607073