Metabolism As a Guiding Force for Immunity

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2019 Jan 4

PMID 30602764

Citations 148

Authors

Jonathan Jung

Hu Zeng

Tiffany Horng

Affiliations

Soon will be listed here.

Abstract

Recent studies indicate that cellular metabolism plays a key role in supporting immune cell maintenance and development. Here, we review how metabolism guides immune cell activation and differentiation to distinct cellular states, and how differential regulation of metabolism allows for context-dependent support during activation and lineage commitment. We discuss emerging principles of metabolic support of immune cell function in physiology and disease, as well as their general relevance to the field of cell biology.

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References

Geltink R, Kyle R, Pearce E . Unraveling the Complex Interplay Between T Cell Metabolism and Function. Annu Rev Immunol. 2018; 36:461-488. PMC: 6323527. DOI: 10.1146/annurev-immunol-042617-053019. View

Davies L, Jenkins S, Allen J, Taylor P . Tissue-resident macrophages. Nat Immunol. 2013; 14(10):986-95. PMC: 4045180. DOI: 10.1038/ni.2705. View

Murray P, Wynn T . Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011; 11(11):723-37. PMC: 3422549. DOI: 10.1038/nri3073. View

Ginhoux F, Schultze J, Murray P, Ochando J, Biswas S . New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat Immunol. 2015; 17(1):34-40. DOI: 10.1038/ni.3324. View

ONeill L, Pearce E . Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2015; 213(1):15-23. PMC: 4710204. DOI: 10.1084/jem.20151570. View

Fukuzumi M, Shinomiya H, Shimizu Y, Ohishi K, Utsumi S . Endotoxin-induced enhancement of glucose influx into murine peritoneal macrophages via GLUT1. Infect Immun. 1996; 64(1):108-12. PMC: 173734. DOI: 10.1128/iai.64.1.108-112.1996. View

Frauwirth K, Riley J, Harris M, Parry R, Rathmell J, Plas D . The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002; 16(6):769-77. DOI: 10.1016/s1074-7613(02)00323-0. View

Doughty C, Bleiman B, Wagner D, Dufort F, Mataraza J, Roberts M . Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth. Blood. 2006; 107(11):4458-65. PMC: 1895797. DOI: 10.1182/blood-2005-12-4788. View

Donnelly R, Loftus R, Keating S, Liou K, Biron C, Gardiner C . mTORC1-dependent metabolic reprogramming is a prerequisite for NK cell effector function. J Immunol. 2014; 193(9):4477-84. PMC: 4201970. DOI: 10.4049/jimmunol.1401558. View

10.

Cramer T, Yamanishi Y, Clausen B, Forster I, Pawlinski R, Mackman N . HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell. 2003; 112(5):645-57. PMC: 4480774. DOI: 10.1016/s0092-8674(03)00154-5. View

11.

Rodriguez-Prados J, Traves P, Cuenca J, Rico D, Aragones J, Martin-Sanz P . Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol. 2010; 185(1):605-14. DOI: 10.4049/jimmunol.0901698. View

12.

Cheng S, Quintin J, Cramer R, Shepardson K, Saeed S, Kumar V . mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014; 345(6204):1250684. PMC: 4226238. DOI: 10.1126/science.1250684. View

13.

Palsson-McDermott E, Curtis A, Goel G, Lauterbach M, Sheedy F, Gleeson L . Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015; 21(1):65-80. PMC: 5198835. DOI: 10.1016/j.cmet.2014.12.005. View

14.

Kornberg M, Bhargava P, Kim P, Putluri V, Snowman A, Putluri N . Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science. 2018; 360(6387):449-453. PMC: 5924419. DOI: 10.1126/science.aan4665. View

15.

Thwe P, Pelgrom L, Cooper R, Beauchamp S, Reisz J, DAlessandro A . Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses. Cell Metab. 2017; 26(3):558-567.e5. PMC: 5657596. DOI: 10.1016/j.cmet.2017.08.012. View

16.

Ip W, Hoshi N, Shouval D, Snapper S, Medzhitov R . Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science. 2017; 356(6337):513-519. PMC: 6260791. DOI: 10.1126/science.aal3535. View

17.

Zigmond E, Bernshtein B, Friedlander G, Walker C, Yona S, Kim K . Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity. 2014; 40(5):720-33. DOI: 10.1016/j.immuni.2014.03.012. View

18.

Drapier J, Hibbs Jr J . Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J Immunol. 1988; 140(8):2829-38. View

19.

Everts B, Amiel E, van der Windt G, Freitas T, Chott R, Yarasheski K . Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood. 2012; 120(7):1422-31. PMC: 3423780. DOI: 10.1182/blood-2012-03-419747. View

20.

Bogdan C . Nitric oxide and the immune response. Nat Immunol. 2001; 2(10):907-16. DOI: 10.1038/ni1001-907. View