Triacylglycerol synthesis enhances macrophage inflammatory function

被引：186

作者：

Castoldi, Angela ^{[1
,2
]}

Monteiro, Lauar B. ^{[1
]}

Bakker, Nikki van Teijlingen ^{[1
,4
]}

Sanin, David E. ^{[1
]}

Rana, Nisha ^{[1
]}

Corrado, Mauro ^{[1
]}

Cameron, Alanna M. ^{[1
]}

Haessler, Fabian ^{[1
]}

Matsushita, Mai ^{[1
]}

Caputa, George ^{[1
]}

Geltink, Ramon I. Klein ^{[1
]}

Buescher, Joerg ^{[3
]}

Edwards-Hicks, Joy ^{[1
]}

Pearce, Erika L. ^{[1
]}

Pearce, Edward J. ^{[1
,4
]}

机构：

[1] Max Planck Inst Epigenet & Immunobiol, Dept Immunometab, Freiburg, Germany

[2] Univ Estadual Campinas, Dept Genet Evolut Microbiol & Immunol, Lab Immunometab, Campinas, SP, Brazil

[3] Max Planck Inst Epigenet & Immunobiol, Metabol Facil, Freiburg, Germany

[4] Univ Freiburg, Fac Biol, Freiburg, Germany

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

巴西圣保罗研究基金会; 日本学术振兴会;

关键词：

DENDRITIC CELL; FOAM CELL; ACCUMULATION; ADIPOCYTES; PATTERNS; STRESS; ROLES; DGAT1;

D O I：

10.1038/s41467-020-17881-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which prevents LD development, has marked effects on the production of inflammatory mediators, including IL-1 beta, IL-6 and PGE2, and on phagocytic capacity. The failure of inflammatory macrophages to make PGE2 when TG-synthesis is inhibited is critical for this phenotype, as addition of exogenous PGE2 is able to reverse the anti-inflammatory effects of TG synthesis inhibition. These findings place LDs in a position of central importance in inflammatory macrophage activation.

引用

页数：11

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