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

   

Authors:	Su, X.; Yu, Y.; Zhong, Y.; Giannopoulou, E. G.; Hu, X.; Liu, H.; Cross, J. R.; Rätsch, G.; Rice, C. M.; Ivashkiv, L. B.
Article Title:	Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation
Abstract:	Interferon-γ (IFN-γ) 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-γ 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 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 showed that IFN-γ selectively modulated the macrophage translatome to promote inflammation, further reprogram metabolic pathways and modulate protein synthesis. These results show that IFN-γ-mediated metabolic reprogramming and translational regulation are key components of classical inflammatory macrophage activation. © 2015, Nature Publishing Group. All rights reserved.
Keywords:	controlled study; protein expression; protein phosphorylation; unclassified drug; human cell; protein localization; translation initiation; inflammation; genetic association; transcription factor hes 1; gamma interferon; messenger rna; gene repression; initiation factor 4e; immunomodulation; down regulation; monocyte; autophagy; macrophage; cell metabolism; phosphotransferase; toll like receptor 2; metabolic regulation; lysosome membrane; ribosome; mammalian target of rapamycin complex 1; macrophage activation; translation regulation; human; priority journal; article; mapk interacting kinase
Journal Title:	Nature Immunology
Volume:	16
Issue:	8
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Date Published:	2015-08-01
Start Page:	838
End Page:	849
Language:	English
DOI:	10.1038/ni.3205
PROVIDER:	scopus
PMCID:	PMC4509841
PUBMED:	26147685
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84937815252&partnerID=40&md5=35b329b401156958a982f13694b278fc
Notes:	Export Date: 2 September 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/79880