Publications and Research
Title
Interferon-γ Regulates Cellular Metabolism and mRNA Translation to Potentiate Macrophage Activation
Document Type
Article
Publication Date
6-29-2015
Abstract
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.
Recommended Citation
Su, Xiaodi; Yu, Yingpu; Zhong, Yi; Giannopoulou, Eugenia; Hu, Xiaoyu; Liu, Hui; Cross, Justin R.; Rätsch, Gunnar; Rice, Charles M.; and Ivashkiv, Lionel B., "Interferon-γ Regulates Cellular Metabolism and mRNA Translation to Potentiate Macrophage Activation" (2015). CUNY Academic Works.
https://academicworks.cuny.edu/ny_pubs/254
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons
Comments
This article was originally published in Nature Immunology, available at doi:10.1038/ni.3205.
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