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      Control of macrophage metabolism and activation by mTOR and Akt signaling.

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          Abstract

          Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies.

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          Author and article information

          Journal
          Semin. Immunol.
          Seminars in immunology
          1096-3618
          1044-5323
          Aug 2015
          : 27
          : 4
          Affiliations
          [1 ] Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, 655 Huntington Ave, II-115, Boston, MA 02115, USA.
          [2 ] Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, 655 Huntington Ave, II-115, Boston, MA 02115, USA. Electronic address: thorng@hsph.harvard.edu.
          Article
          S1044-5323(15)00063-9 NIHMS744244
          10.1016/j.smim.2015.08.001
          26360589
          34551adf-dcb9-4710-a2eb-1ebcd0c73947
          Copyright © 2015 Elsevier Ltd. All rights reserved.
          History

          Akt,Immunometabolism,Macrophage activation,Macrophage metabolism,mTOR

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