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

Stanley Ching Cheng Huang, Bart Everts, Yulia Ivanova, David O'Sullivan, Marcia Nascimento, Amber M. Smith, Wandy Beatty, Latisha Love-Gregory, Wing Y. Lam, Christina M. O'Neill, Cong Yan, Hong Du, Nada A. Abumrad, Joseph F. Urban, Maxim N. Artyomov, Erika L. Pearce, Edward J. Pearce

Research output: Contribution to journalArticle

310 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)846-855
Number of pages10
JournalNature Immunology
Volume15
Issue number9
DOIs
StatePublished - 2014

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Macrophage Activation
Lipolysis
Fatty Acids
Interleukin-4 Receptors
Sterol Esterase
Scavenger Receptors
Helminths
Oxidative Phosphorylation
Wound Healing
Immunity
Atherosclerosis
Parasites
Triglycerides
Homeostasis
Gene Expression
Infection

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Huang, S. C. C., Everts, B., Ivanova, Y., O'Sullivan, D., Nascimento, M., Smith, A. M., ... Pearce, E. J. (2014). Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nature Immunology, 15(9), 846-855. https://doi.org/10.1038/ni.2956

Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. / Huang, Stanley Ching Cheng; Everts, Bart; Ivanova, Yulia; O'Sullivan, David; Nascimento, Marcia; Smith, Amber M.; Beatty, Wandy; Love-Gregory, Latisha; Lam, Wing Y.; O'Neill, Christina M.; Yan, Cong; Du, Hong; Abumrad, Nada A.; Urban, Joseph F.; Artyomov, Maxim N.; Pearce, Erika L.; Pearce, Edward J.

In: Nature Immunology, Vol. 15, No. 9, 2014, p. 846-855.

Research output: Contribution to journalArticle

Huang, SCC, Everts, B, Ivanova, Y, O'Sullivan, D, Nascimento, M, Smith, AM, Beatty, W, Love-Gregory, L, Lam, WY, O'Neill, CM, Yan, C, Du, H, Abumrad, NA, Urban, JF, Artyomov, MN, Pearce, EL & Pearce, EJ 2014, 'Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages', Nature Immunology, vol. 15, no. 9, pp. 846-855. https://doi.org/10.1038/ni.2956
Huang SCC, Everts B, Ivanova Y, O'Sullivan D, Nascimento M, Smith AM et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nature Immunology. 2014;15(9):846-855. https://doi.org/10.1038/ni.2956
Huang, Stanley Ching Cheng ; Everts, Bart ; Ivanova, Yulia ; O'Sullivan, David ; Nascimento, Marcia ; Smith, Amber M. ; Beatty, Wandy ; Love-Gregory, Latisha ; Lam, Wing Y. ; O'Neill, Christina M. ; Yan, Cong ; Du, Hong ; Abumrad, Nada A. ; Urban, Joseph F. ; Artyomov, Maxim N. ; Pearce, Erika L. ; Pearce, Edward J. / Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. In: Nature Immunology. 2014 ; Vol. 15, No. 9. pp. 846-855.
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