Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation.
Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation.
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DOI：
10.1038/ni.3205
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发表时间：
2015-08
影响因子：
30.5
通讯作者：
Ivashkiv LB
中科院分区：
文献类型：
--
作者：
Su X;Yu Y;Zhong Y;Giannopoulou EG;Hu X;Liu H;Cross JR;Rätsch G;Rice CM;Ivashkiv LB
Interferon-γ (IFN-γ) primes macrophages for enhanced inflammatory activation by Toll-like receptors (TLRs) and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-γ regulates human macrophage metabolism and translation by targeting the kinases mTORC1 and MNK that both converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of mTORC1 by IFN-γ was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-γ selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-γ-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation.
