Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells
Abstract
:1. Introduction
2. Metabolic Networks in Lymphoid Cells
2.1. Function and Activation of T Cells
2.2. The Metabolism of Naive/Quiescent T Cells
2.3. Metabolic Switch in Effector T Cells and Its Regulation
2.3.1. Metabolic Reprogramming
2.3.2. Regulators of the Metabolic Switch in Effector T Cells
2.3.3. Metabolic Switch and T Cell Phenotypes
2.4. Metabolic Switch in Memory T Cells
2.4.1. Metabolic Reprogramming
2.4.2. Antigen Recall
2.5. The Metabolism of Regulatory T Cells
3. Metabolic Network in Myeloid Cells
3.1. Metabolic Switch in Macrophages Upon Polarization
3.1.1. Macrophage Differentiation/Subtypes
3.1.2. Metabolic Networks in M1 and M2 Macrophages
3.2. The Metabolism of Dendritic Cells
3.2.1. Function
3.2.2. Metabolic Network in DCs
4. The Emergence of Specific Metabolic Targets to Modulate Immune Cell Effector Functions
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
- Macintyre, A.N.; Rathmell, J.C. Activated lymphocytes as a metabolic model for carcinogenesis. Cancer Metab. 2015, 1, 5. [Google Scholar] [CrossRef] [PubMed]
- Anderson, N.M.; Mucka, P.; Kern, J.G.; Feng, H. The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell 2017, 9, 216–237. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Warburg, O. On the origin of cancer cells. Science 1956, 123, 309–314. [Google Scholar] [CrossRef] [PubMed]
- Lunt, S.Y.; Vander Heiden, M.G. Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 2011, 27, 441–464. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Morin, A.; Letouzé, E.; Gimenez-Roqueplo, A.-P.; Favier, J. Oncometabolites-driven tumorigenesis: From genetics to targeted therapy. Int. J. Cancer 2014, 135, 2237–2248. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Patra, K.C.; Hay, N. The pentose phosphate pathway and cancer. Trends Biochem. Sci. 2014, 39, 347–354. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Janeway, C.A.; Travers, P.; Walport, M. Immunobiology, 5th ed.; Garland Science: New York, NY, USA, 2011. [Google Scholar]
- Fox, C.J.; Hammerman, P.S.; Thompson, C.B. Fuel feeds function: Energy metabolism and the T-cell response. Nat. Rev. Immunol. 2005, 5, 844–852. [Google Scholar] [CrossRef] [PubMed]
- Pearce, E.L.; Pearce, E.J. Metabolic pathways in immune cell activation and quiescence. Immunity 2013, 38, 633–643. [Google Scholar] [CrossRef] [PubMed]
- Van der Windt, G.J.W.; Everts, B.; Chang, C.-H.; Curtis, J.D.; Freitas, T.C.; Amiel, E.; Pearce, E.J.; Pearce, E.L. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 2012, 36, 68–78. [Google Scholar] [CrossRef] [PubMed]
- Plas, D.R.; Rathmell, J.C.; Thompson, C.B. Homeostatic control of lymphocyte survival: Potential origins and implications. Nat. Immunol. 2002, 3, 515–521. [Google Scholar] [CrossRef] [PubMed]
- Tan, J.T.; Dudl, E.; LeRoy, E.; Murray, R.; Sprent, J.; Weinberg, K.I.; Suurh, C.D. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc. Natl. Acad. Sci. USA 2001, 98, 8732–8737. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Rathmell, J.C.; Vander Heiden, M.G.; Harris, M.H.; Frauwirth, K.A.; Tompson, C.B. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol. Cell 2000, 6, 683–692. [Google Scholar] [CrossRef]
- Yang, K.; Neale, G.; Green, D.R.; He, W.; Chi, H. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat. Immunol. 2011, 12, 888–897. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Maciolek, J.A.; Pasternak, J.A.; Wilson, H.L. Metabolism of activated T lymphocytes. Curr. Opin. Immunol. 2014, 27, 60–74. [Google Scholar] [CrossRef] [PubMed]
- Michalek, R.D.; Gerriets, V.A.; Jacobs, S.R. Cutting edge: Distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol. 2011, 186, 3299–3303. [Google Scholar] [CrossRef] [PubMed]
- Sena, L.A.; Li, S.; Jairaman, A.; Prakriya, M.; Ezponda, T.; Hildeman, D.A.; Wang, C.R.; Schumacker, P.T.; Licht, J.D.; Perlman, H.; et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 2013, 38, 225–236. [Google Scholar] [CrossRef] [PubMed]
- Van der Windt, G.J.W.; O’Sullivan, D.; Everts, B.; Stanley, C.-C.H.; Buck, M.D.; Curtis, J.D.; Chang, C.-H.; Smith, A.M.; Ai, T.; Faubert, B.; et al. CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability. Proc. Natl. Acad. Sci. USA 2013, 110, 14336–14341. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Finlay, D.K.; Rosenzweig, E.; Sinclair, L.V.; Feijoo-Carnero, C.; Hukelmann, J.L.; Rolf, J.; Panteleyev, A.A.; Okkenhaug, K.; Cantrell, D.A. PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J. Exp. Med. 2012, 209, 2441–2453. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kim, J.; Tchernyshyov, I.; Semenza, G.L.; Dang, C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006, 3, 177–185. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Greiner, E.F.; Guppy, M.; Brand, K. Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. J. Biol. Chem. 1994, 269, 31484–31490. [Google Scholar] [PubMed]
- Anastasiou, D.; Poulogiannis, G.; Asara, J.M.; Boxer, M.B.; Jiang, J.K.; Shen, M.; Bellinger, G.; Sasaki, A.T.; Locasale, J.W.; Auld, D.S.; et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011, 334, 1278–1283. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Carr, E.L.; Kelman, A.; Wu, G.S.; Gopaul, R.; Senkevittch, E.; Aghvanyan, A.; Turay, A.M.; Frauwirth, K.A. Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J. Immunol. 2010, 185, 1037–1044. [Google Scholar] [CrossRef] [PubMed]
- Macintyre, A.N.; Gerriets, V.A.; Nichols, A.G.; Michalek, R.D.; Rudolph, M.C.; Deoliveira, D.; Anderson, S.M.; Abel, E.D.; Chen, B.J.; Hale, L.P.; et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 2014, 20, 61–72. [Google Scholar] [CrossRef] [PubMed]
- Sinclair, L.V.; Rolf, J.; Emslie, E.; Shi, Y.-B.; Taylor, P.M.; Cantrell, D.A. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat. Immunol. 2013, 14, 500–508. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Chang, C.-H.; Curtis, J.D.; Maggi, L.B.; Faubert, B.; Villarino, A.V.; O’Sullivan, D.; Ching-Cheng Huang, S.; van der Windt, G.J.W.; Blagih, J.; Qiu, J.; et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 2013, 153, 1239–1251. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, S.R.; Herman, C.E.; Maciver, N.J.; Wofford, J.A.; Wieman, H.L.; Hammen, J.J.; Rathmell, J.C. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 2008, 180, 4476–4486. [Google Scholar] [CrossRef] [PubMed]
- Tan, H.; Yang, K.; Li, Y.; Shaw, T.I.; Wang, Y.; Blanco, D.B.; Wang, X.; Cho, J.H.; Wang, H.; Rankin, S.; et al. Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation. Immunity 2017, 46, 488–503. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Wang, R.; Dillon, C.P.; Shi, L.Z.; Milasta, S.; Carter, R.; Finkelstein, D.; McCormick, L.L.; Fitzgerald, P.; Chi, H.; Munger, J.; et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 2011, 35, 871–882. [Google Scholar] [CrossRef] [PubMed]
- Jones, R.G.; Thompson, C.B. Revving the Engine: Signal Transduction Fuels T Cell Activation. Immunity 2007, 27, 173–178. [Google Scholar] [CrossRef] [PubMed][Green Version]
- O’Sullivan, D.; Pearce, E.L. Targeting T cell metabolism for therapy. Trends Immunol. 2015, 36, 71–80. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Lee, J.; Walsh, M.C.; Hoehn, K.L.; James, D.E.; John Wherry, E.; Choi, Y. Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity. J. Immunol. 2014, 192, 3190–3199. [Google Scholar] [CrossRef] [PubMed]
- Gaber, T.; Strehl, C.; Sawitzki, B.; Hoff, P.; Buttgereit, F. Cellular Energy Metabolism in T-Lymphocytes. Int. Rev. Immunol. 2015, 34, 34–49. [Google Scholar] [CrossRef] [PubMed]
- Altman, B.J.; Dang, C.V. Normal and cancer cell metabolism: Lymphocytes and lymphoma. FEBS J. 2012, 279, 2598–2609. [Google Scholar] [CrossRef] [PubMed]
- Michalek, R.D.; Gerriets, V.A.; Nichols, A.G.; Inoue, M.; Kazmin, D.; Chang, C.-Y.; Dwyer, M.A.; Nelson, E.R.; Pollizzi, K.N.; Ilkayeva, O.; et al. Estrogen-related receptor-α is a metabolic regulator of effector T-cell activation and differentiation. Proc. Natl. Acad. Sci. USA 2011, 108, 18348–18353. [Google Scholar] [CrossRef] [PubMed]
- Frauwirth, K.A.; Riley, J.L.; Harris, M.H.; Parry, R.V.; Rathmell, J.C.; Plas, D.R.; Elstrom, R.L.; June, C.H.; Thompson, C.B. The CD28 signaling pathway regulates glucose metabolism. Immunity 2002, 16, 769–777. [Google Scholar] [CrossRef]
- Powell, J.D.; Pollizzi, K.N.; Heikamp, E.B.; Horton, M.R. Regulation of immune responses by mTOR. Annu. Rev. Immunol. 2012, 30, 39–68. [Google Scholar] [CrossRef] [PubMed]
- MacIver, N.J.; Michalek, R.D.; Rathmell, J.C. Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 2013, 31, 259–283. [Google Scholar] [CrossRef] [PubMed]
- Powell, J.D.; Delgoffe, G.M. The mammalian target of rapamycin: Linking T cell differentiation, function, and metabolism. Immunity 2010, 33, 301–311. [Google Scholar] [CrossRef] [PubMed]
- Tandon, P.; Gallo, C.A.; Khatri, S.; Barger, J.F.; Yepiskoposyan, H.; Plas, D.R. Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency. Proc. Natl. Acad. Sci. USA 2011, 108, 2361–2365. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Hardie, D.G.; Ross, F.A.; Hawley, S.A. AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 2012, 13, 251–262. [Google Scholar] [CrossRef] [PubMed][Green Version]
- MacIver, N.J.; Blagih, J.; Saucillo, D.C.; Tonelli, L.; Griss, T.; Rathmell, J.C.; Jones, R.G. The liver kinase B1 is a central regulator of T cell development, activation, and metabolism. J. Immunol. 2011, 187, 4187–4198. [Google Scholar] [CrossRef] [PubMed]
- Rolf, J.; Zarrouk, M.; Finlay, D.K.; Foretz, M.; Viollet, B.; Cantrell, D.A. AMPKα1: A glucose sensor that controls CD8 T-cell memory. Eur. J. Immunol. 2013, 43, 889–896. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Blagih, J.; Coulombe, F.; Vincent, E.E.; Dupuy, F.; Galicia-Vazquez, G.; Yurchenko, E.; Raissi, T.C.; van der Windt, G.J.; Viollet, B.; Pearce, E.L.; et al. The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. Immunity 2015, 42, 41–54. [Google Scholar] [CrossRef] [PubMed]
- Doedens, A.L.; Phan, A.T.; Stradner, M.H.; Fujimoto, J.K.; Nguyen, J.V.; Yang, E.; Johnson, R.S.; Goldrath, A.W. Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen. Nat. Immunol. 2013, 14, 1173–1182. [Google Scholar] [CrossRef] [PubMed]
- Tyrakis, P.A.; Palazon, A.; Macias, D.; Lee, K.L.; Phan, A.T.; Velica, P.; You, J.; Chia, G.S.; Sim, J.; Doedens, A.; et al. S-2-hydroxyglutarate regulates CD8(+) T-lymphocyte fate. Nature 2016, 540, 236–241. [Google Scholar] [CrossRef] [PubMed]
- Delgoffe, G.M.; Powell, J.D. mTOR: Taking cues from the immune microenvironment. Immunology 2009, 127, 459–465. [Google Scholar] [CrossRef] [PubMed]
- Kopf, H.; de la Rosa, G.M.; Howard, O.M.Z.; Chen, X. Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int. Immunopharmacol. 2007, 7, 1819–1824. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Dang, E.V.; Barbi, J.; Yang, H.-Y.; Jinasena, D.; Yu, H.; Zheng, Y.; Bordman, Z.; Fu, J.; Kim, Y.; Yen, H.R.; et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 2011, 146, 772–784. [Google Scholar] [CrossRef] [PubMed]
- Shi, L.Z.; Wang, R.; Huang, G.; Vogel, P.; Neale, G.; Green, D.R.; Chi, H. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 2011, 208, 1367–1376. [Google Scholar] [CrossRef] [PubMed]
- Delgoffe, G.M.; Pollizzi, K.N.; Waickman, A.T.; Heikamp, E.; Meyers, D.J.; Horton, M.R.; Xiao, B.; Worley, P.F.; Powell, J.D. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 2011, 12, 295–303. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Lee, K.; Gudapati, P.; Dragovic, S.; Spencer, C.; Joyce, S.; Killeen, N.; Magnuson, M.A.; Boothby, M. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 2010, 32, 743–753. [Google Scholar] [CrossRef] [PubMed]
- Peng, M.; Yin, N.; Chhangawala, S.; Xu, K.; Leslie, C.S.; Li, M.O. Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science 2016, 354, 481–484. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Ho, P.-C.; Bihuniak, J.D.; Macintyre, A.N.; Staron, M.; Liu, X.; Amezquita, R.; Tsui, Y.-C.; Cui, G.; Micevic, G.; Perales, J.C.; et al. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Cell 2015, 162, 1217–1228. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Ron-Harel, N.; Santos, D.; Ghergurovich, J.M.; Sage, P.T.; Reddy, A.; Lovitch, S.B.; Dephoure, N.; Satterstrom, F.K.; Sheffer, M.; Spinelli, J.B.; et al. Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation. Cell Metab. 2016, 24, 104–117. [Google Scholar] [CrossRef] [PubMed]
- Yoshida, K.; Maekawa, T.; Zhu, Y.; Renard-Guillet, C.; Chatton, B.; Inoue, K.; Uchiyama, T.; Ishibashi, K.; Yamada, T.; Ohno, N.; et al. The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory. Nat. Immunol. 2015, 16, 1034–1043. [Google Scholar] [CrossRef] [PubMed]
- Procaccini, C.; Carbone, F.; Di Silvestre, D.; Brambilla, F.; De Rosa, V.; Galgani, M.; Faicchia, D.; Marone, D.; Tramontano, D.; Corona, M.; et al. The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements. Immunity 2016, 44, 406–421. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Pearce, E.L.; Walsh, M.C.; Cejas, P.J.; Harms, G.M.; Shen, H.; Wang, L.-S.; Jones, R.G.; Choi, Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009, 460, 103–107. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Fraser, K.A.; Schenkel, J.M.; Jameson, S.C.; Vezys, V.; Masopust, D. Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. Immunity 2013, 39, 171–183. [Google Scholar] [CrossRef] [PubMed]
- Gubser, P.M.; Bantug, G.R.; Razik, L.; Fischer, M.; Dimeloe, S.; Hoenger, G.; Durovic, D.; Jauch, A.; Hess, C. Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch. Nat. Immunol. 2013, 14, 1064–1072. [Google Scholar] [CrossRef] [PubMed]
- Balmer, M.L.; Ma, E.H.; Bantug, G.R.; Grählert, J.; Pfister, S.; Glatter, T.; Jauch, A.; Dimeloe, S.; Slack, E.; Dehio, P.; et al. Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function. Immunity 2016, 44, 1312–1324. [Google Scholar] [CrossRef] [PubMed]
- Klebanoff, C.A.; Gattinoni, L.; Torabi-Parizi, P.; Kerstann, K.; Cardones, A.R.; Finkelstein, S.E.; Palmer, D.C.; Antony, P.A.; Hwang, S.T.; Rosenberg, S.A.; et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc. Natl. Acad. Sci. USA 2005, 102, 9571–9576. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Buck, M.D.; O’Sullivan, D.; Klein Geltink, R.I.; Curtis, J.D.; Chang, C.-H.; Sanin, D.E.; Qiu, J.; Kretz, O.; Braas, D.; van der Windt, G.J.W.; et al. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming. Cell 2016, 166, 63–76. [Google Scholar] [CrossRef] [PubMed]
- Scharping, N.E.; Menk, A.V.; Moreci, R.S.; Whetstone, R.D.; Dadey, R.E.; Watkins, S.C.; Ferris, R.L.; Delgoffe, G.M. The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction. Immunity 2016, 45, 701–703. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Geiger, R.; Rieckmann, J.C.; Wolf, T.; Basso, C.; Feng, Y.; Fuhrer, T.; Kogadeeva, M.; Picotti, P.; Meissner, F.; Mann, M.; et al. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell 2016, 167, 829–842.e13. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Champagne, D.P.; Hatle, K.M.; Fortner, K.A.; D’Alessandro, A.; Thornton, T.M.; Yang, R.; Torralba, D.; Tomás-Cortázar, J.; Jun, Y.W.; Ahn, K.H.; et al. Fine-Tuning of CD8(+) T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus. Immunity 2016, 44, 1299–1311. [Google Scholar] [CrossRef] [PubMed]
- Zeng, H.; Yang, K.; Cloer, C.; Neale, G.; Vogel, P.; Chi, H. mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature 2013, 499, 485–490. [Google Scholar] [CrossRef] [PubMed]
- Newton, R.; Priyadharshini, B.; Turka, L.A. Immunometabolism of regulatory T cells. Nat. Immunol. 2016, 17, 618–625. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Sharma, M.D.; Shinde, R.; McGaha, T.L.; Huang, L.; Holmgaard, R.B.; Wolchok, J.D.; Mautino, M.R.; Celis, E.; Sharpe, A.H.; Francisco, L.M.; et al. The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment. Sci. Adv. 2015, 1, e1500845. [Google Scholar] [CrossRef] [PubMed]
- Palucka, A.K.; Coussens, L.M. The Basis of Oncoimmunology. Cell 2016, 164, 1233–1247. [Google Scholar] [CrossRef] [PubMed]
- Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived-suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009, 9, 162–174. [Google Scholar] [CrossRef] [PubMed]
- Biswas, S.K. Metabolic Reprogramming of Immune Cells in Cancer Progression. Immunity 2015, 43, 435–449. [Google Scholar] [CrossRef] [PubMed]
- Biswas, S.K.; Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat. Immunol. 2010, 11, 889–896. [Google Scholar] [CrossRef] [PubMed]
- Murray, P.J.; Wynn, T.A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 2011, 11, 723–737. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Duluc, D.; Corvaisier, M.; Blanchard, S.; Catala, L.; Descamps, P.; Gamelin, E.; Ponsoda, S.; Delneste, Y.; Hebbar, M.; Jeannin, P. Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. Int. J. Cancer 2009, 125, 367–373. [Google Scholar] [CrossRef] [PubMed]
- Biswas, S.K.; Allavena, P.; Mantovani, A. Tumor-associated macrophages: Functional diversity, clinical significance, and open questions. Semin. Immunopathol. 2013, 35, 585–600. [Google Scholar] [CrossRef] [PubMed]
- Colegio, O.R.; Chu, N.-Q.; Szabo, A.L.; Chu, T.; Rhebergen, A.M.; Jairam, V.; Cyrus, N.; Brokowski, C.E.; Eisenbarth, S.C.; Phillips, G.M.; et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 2014, 513, 559–563. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Ohashi, T.; Aoki, M.; Tomita, H.; Akazawa, T.; Sato, K.; Kuze, B.; Mizuta, K.; Hara, A.; Nagaoka, H.; Inoue, N.; et al. M2-like macrophage polarization in high lactic acid-producing head and neck cancer. Cancer Sci. 2017, 108, 1128–1134. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Zhao, Y.; Wang, D.; Xu, T.; Liu, P.; Cao, Y.; Wang, Y.; Yang, X.; Xu, X.; Wang, X.; Niu, H. Bladder cancer cells re-educate TAMs through lactate shuttling in the microfluidic cancer microenvironment. Oncotarget 2015, 6, 39196–39210. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Dietl, K.; Renner, K.; Dettmer, K.; Timischl, B.; Eberhart, K.; Dorn, C.; Hellerbrand, C.; Kastenberger, M.; Kunz-Schughart, L.A.; Oefner, P.J.; et al. Lactic acid and acidification inhibit TNF secretion and glycolysis of human monocytes. J. Immunol. 2010, 184, 1200–1209. [Google Scholar] [CrossRef] [PubMed]
- Mills, E.L.; Kelly, B.; Logan, A.; Costa, A.S.H.; Varma, M.; Bryant, C.E.; Tourlomousis, P.; Däbritz, J.H.M.; Gottlieb, E.; Latorre, I.; et al. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell 2016, 167, 457–470.e13. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Huang, S.C.-C.; Smith, A.M.; Everts, B.; Colonna, M.; Pearce, E.L.; Schilling, J.D.; Pearce, E.J. Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation. Immunity 2016, 45, 817–830. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Pello, O.M.; De Pizzol, M.; Mirolo, M.; Soucek, L.; Zammataro, L.; Amabile, A.; Doni, A.; Nebuloni, M.; Swigart, L.B.; Evan, G.I.; et al. Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood 2012, 119, 411–421. [Google Scholar] [CrossRef] [PubMed]
- Cramer, T.; Yamanishi, Y.; Clausen, B.E.; Förster, I.; Pawlinski, R.; Mackman, N.; Haase, V.H.; Jaenisch, R.; Corr, M.; Nizet, V.; et al. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 2003, 112, 645–657. [Google Scholar] [CrossRef]
- Li, L.; Ng, D.S.W.; Mah, W.-C.; Almeida, F.F.; Rahmat, S.A.; Rao, V.K.; Leow, S.C.; Laudisi, F.; Peh, M.T.; Goh, A.M.; et al. A unique role for p53 in the regulation of M2 macrophage polarization. Cell Death Differ. 2015, 22, 1081–1093. [Google Scholar] [CrossRef] [PubMed]
- Peyssonnaux, C.; Datta, V.; Cramer, T.; Doedens, A.; Theodorakis, E.A.; Gallo, R.L.; Hurtado-Ziola, N.; Nizet, V.; Johnson, R.S. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J. Clin. Investig. 2005, 115, 1806–1815. [Google Scholar] [CrossRef] [PubMed]
- Vats, D.; Mukundan, L.; Odegaard, J.I.; Zhang, L.; Smith, K.L.; Morel, C.R.; Wagner, R.A.; Greaves, D.R.; Murray, P.J.; Chawla, A. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab. 2006, 4, 13–24. [Google Scholar] [CrossRef] [PubMed]
- Jha, A.K.; Huang, S.C.-C.; Sergushichev, A.; Lampropoulou, V.; Ivanova, Y.; Loginicheva, E.; Chmielewski, K.; Stewart, K.M.; Ashall, J.; Everts, B.; et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 2015, 42, 419–430. [Google Scholar] [CrossRef] [PubMed]
- Odegaard, J.I. Chawla A Alternative macrophage activation and metabolism. Annu. Rev. Pathol. 2011, 6, 275–297. [Google Scholar] [CrossRef] [PubMed]
- Arts, R.J.W.; Novakovic, B.; Ter Horst, R.; Carvalho, A.; Bekkering, S.; Lachmandas, E.; Rodrigues, F.; Silvestre, R.; Cheng, S.-C.; Wang, S.-Y.; et al. Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. Cell Metab. 2016, 24, 807–819. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Netea, M.G.; Joosten, L.A.B.; Latz, E.; Mills, K.H.G.; Natoli, G.; Stunnenberg, H.G.; O’Neill, L.A.J.; Xavier, R.J. Trained immunity: A program of innate immune memory in health and disease. Science 2016, 352, aaf1098. [Google Scholar] [CrossRef] [PubMed]
- Krawczyk, C.M.; Holowka, T.; Sun, J.; Blagih, J.; Amiel, E.; DeBerardinis, R.J.; Cross, J.R.; Jung, E.; Thompson, C.B.; Jones, R.G.; et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 2010, 115, 4742–4749. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Jantsch, J.; Chakravortty, D.; Turza, N.; Prechtel, A.T.; Buchholz, B.; Gerlach, R.G.; Volke, M.; Gläsner, J.; Warnecke, C.; Wiesener, M.S.; et al. Hypoxia and hypoxia-inducible factor-1 alpha modulate lipopolysaccharide-induced dendritic cell activation and function. J. Immunol. 2008, 180, 4697–4705. [Google Scholar] [CrossRef] [PubMed]
- Mancino, A.; Schioppa, T.; Larghi, P.; Pasqualini, F.; Nebuloni, M.; Chen, I.-H.; Sozzani, S.; Austyn, J.M.; Mantovani, A.; Sica, A. Divergent effects of hypoxia on dendritic cell functions. Blood 2008, 112, 3723–3734. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Yang, M.; Ma, C.; Liu, S.; Shao, Q.; Gao, W.; Song, B.; Sun, J.; Xie, Q.; Zhang, Y.; Feng, A.; et al. HIF-dependent induction of adenosine receptor A2b skews human dendritic cells to a Th2-stimulating phenotype under hypoxia. Immunol. Cell Biol. 2010, 88, 165–171. [Google Scholar] [CrossRef] [PubMed]
- Novitskiy, S.V.; Ryzhov, S.; Zaynagetdinov, R.; Goldstein, A.E.; Huang, Y.; Tikhomirov, O.Y.; Blackburn, M.R.; Biaggioni, I.; Carbone, D.P.; Feoktistov, I.; et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 2008, 112, 1822–1831. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kawalekar, O.U.; O’Connor, R.S.; Fraietta, J.A.; Guo, L.; McGettigan, S.E.; Posey, A.D.; Patel, P.R.; Guedan, S.; Scholler, J.; Keith, B.; et al. Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. Immunity 2016, 44, 380–390. [Google Scholar] [CrossRef] [PubMed]
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Domblides, C.; Lartigue, L.; Faustin, B. Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells. Cells 2018, 7, 68. https://doi.org/10.3390/cells7070068
Domblides C, Lartigue L, Faustin B. Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells. Cells. 2018; 7(7):68. https://doi.org/10.3390/cells7070068
Chicago/Turabian StyleDomblides, Charlotte, Lydia Lartigue, and Benjamin Faustin. 2018. "Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells" Cells 7, no. 7: 68. https://doi.org/10.3390/cells7070068