Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation

被引：238

作者：

Su, Xiaodi ^{[1
,2
,3
]}

Yu, Yingpu ^{[4
]}

Zhong, Yi ^{[5
]}

Giannopoulou, Eugenia G. ^{[2
,3
,6
]}

Hu, Xiaoyu ^{[2
,3
]}

Liu, Hui ^{[7
]}

Cross, Justin R. ^{[7
]}

Raetsch, Gunnar ^{[5
]}

Rice, Charles M. ^{[4
]}

Ivashkiv, Lionel B. ^{[1
,2
,3
]}

机构：

[1] Weill Cornell Grad Sch Med Sci, Grad Program Immunol & Microbial Pathogenesis, New York, NY 10065 USA

[2] Hosp Special Surg, Arthritis & Tissue Degenerat Program, New York, NY 10021 USA

[3] Hosp Special Surg, David Z Rosensweig Genom Res Ctr, New York, NY 10021 USA

[4] Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Computat Biol Dept, New York, NY 10021 USA

[6] CUNY, New York City Coll Technol, Dept Biol Sci, Brooklyn, NY 11210 USA

[7] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, New York, NY 10021 USA

来源：

NATURE IMMUNOLOGY | 2015年 / 16卷 / 08期

关键词：

IMMUNE-RESPONSES; DENDRITIC CELLS; TRYPTOPHAN CATABOLISM; BACTERIAL PATHOGENS; I INTERFERON; MTOR; PATHWAY; POLARIZATION; EXPRESSION; KINASE;

D O I：

10.1038/ni.3205

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Interferon-gamma (IFN-gamma) primes macrophages for enhanced microbial killing and inflammatory activation by Toll-like receptors (TLRs), but little is known about the regulation of cell metabolism or mRNA translation during this priming. We found that IFN-gamma regulated the metabolism and mRNA translation of human macrophages by targeting the kinases mTORC1 and MNK, both of which converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of mTORC1 byIFN-gamma was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages showed thatIFN-gamma selectively modulated the macrophage translatome to promote inflammation, further reprogram metabolic pathways and modulate protein synthesis. These results show thatIFN-gamma-mediated metabolic reprogramming and translational regulation are key components of classical inflammatory macrophage activation.

引用

页码：838 / +

页数：14

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