Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon...

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Published in:Frontiers in immunology Vol. 12; p. 753092
Main Authors: Wang, Hao, Zheng, Xueyue, Liu, Bingnan, Xia, Yaoyao, Xin, Zhongquan, Deng, Baichuan, He, Liuqin, Deng, Jinping, Ren, Wenkai
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 21-10-2021
Subjects:
Animals
asparagine
aspartate
Aspartic Acid - metabolism
Citrobacter rodentium
Colitis - immunology
Colitis - microbiology
Cytokines - blood
Enterobacteriaceae Infections - immunology
Female
HIF-1α
Hypoxia-Inducible Factor 1, alpha Subunit
Immunology
inflammasome
Inflammasomes - physiology
Interferon-gamma - pharmacology
Interleukin-1beta - biosynthesis
Interleukin-1beta - genetics
Lipopolysaccharides - pharmacology
macrophage
Macrophage Activation
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - immunology
Macrophages, Peritoneal - metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Swine
macrophage
HIF-1α
asparagine
aspartate
inflammasome
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Summary:Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1β (IL-1β) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1α (HIF-1α) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.
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Edited by: Zhenlong Wu, China Agricultural University, China
This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Immunology
Reviewed by: Ko Fujimori, Osaka University of Pharmaceutical Sciences, Japan; Lei Shi, Georgia State University, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.753092