Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic cells by preserving mitochondrial function

Journal of Immunology

Volumn 193, Issue 6, 2014, Pages 2821-2830

  Amiel, Eyal ^a,b   Everts, Bart ^c   Fritz, Daniel ^a   Beauchamp, Saritha ^a   Ge, Burong ^a   Pearce, Erika L ^c   Pearce, Edward J ^c  

^a University of Vermont   (United States)

^b TRUDEAU INSTITUTE   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; FATTY ACID; GLUCOSE; GLUTAMATE SYNTHASE (NADH); INDUCIBLE NITRIC OXIDE SYNTHASE; LIPOPOLYSACCHARIDE; MAMMALIAN TARGET OF RAPAMYCIN; NITRIC OXIDE; MTOR PROTEIN, MOUSE; NOS2 PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; TOLL LIKE RECEPTOR;

ANAEROBIC GLYCOLYSIS; ANIMAL EXPERIMENT; ARTICLE; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL ENERGY; CELL METABOLISM; CELL SURVIVAL; CONTROLLED STUDY; DENDRITIC CELL; DOWN REGULATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; IN VITRO STUDY; IN VIVO STUDY; LIPOLYSIS; LONGEVITY; MACROAUTOPHAGY; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PROTEIN EXPRESSION; T LYMPHOCYTE ACTIVATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; C57BL MOUSE; CELL AGING; CELL CULTURE; GENETIC TRANSCRIPTION; GENETICS; GLYCOLYSIS; IMMUNOLOGY; METABOLISM; MITOCHONDRION; PROTEIN SYNTHESIS; VACCINATION;

ADENOSINE TRIPHOSPHATE; ANIMALS; CELL AGING; CELLS, CULTURED; DENDRITIC CELLS; FATTY ACIDS; GLUCOSE; GLYCOLYSIS; LIPOPOLYSACCHARIDES; MICE; MICE, INBRED C57BL; MITOCHONDRIA; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; OXIDATIVE PHOSPHORYLATION; PROTEIN BIOSYNTHESIS; TOLL-LIKE RECEPTORS; TOR SERINE-THREONINE KINASES; TRANSCRIPTION, GENETIC; VACCINATION;

EID: 84907069550     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1302498     Document Type: Article

References (57)

1. Barton, G. M., and R. Medzhitov. 2002. Control of adaptive immune responses by Toll-like receptors. Curr. Opin. Immunol. 14: 380-383
2. Steinman, R. M., and H. Hemmi. 2006. Dendritic cells: translat ing innate to adaptive immunity. Curr. Top. Microbiol. Immunol. 311: 17-58
3. Akira, S., and K. Takeda. 2004. Toll-like receptor signalling. Nat. Rev. Immunol. 4: 499-511
4. Takeda, K., and S. Akira. 2004. TLR signaling pathways. Semin. Immunol. 16: 3-9
5. Amati, L., M. Pepe, M. E. Passeri, M. L. Mastronardi, E. Jirillo, and V. Covelli. 2006. Toll-like receptor signaling mechanisms involved in dendritic cell activation: potential therapeutic control of T cell polarization. Curr. Pharm. Des. 12: 4247-4254
6. Everts, B., E. Amiel, G. J. van der Windt, T. C. Freitas, R. Chott, K. E. Yarasheski, E. L. Pearce, and E. J. Pearce. 2012. Commitment to glycolysis sustains survival of NO-producing inflammatory dendriti c cells. Blood 120: 1422-1431
7. Krawczyk, C. M., T. Holowka, J. Sun, J. Blagih, E. Amiel, R. J. DeBerardinis, J. R. Cross, E. Jung, C. B. Thompson, R. G. Jones, and E. J. Pea rce. 2010. Tolllike receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115: 4742-4749
8. Amiel, E., B. Everts, T. C. Freitas, I. L. King, J. D. Curtis, E. L. Pearce, and E. J. Pearce. 2012. Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J. Immunol. 189: 2151-2158
9. Gulati, P., and G. Thomas. 2007. Nutrient sensing in the mTOR/S6K1 signalling pathway. Biochem. Soc. Trans. 35: 236-238
10. Kapahi, P., D. Chen, A. N. Rogers, S. D. Katewa, P. W. Li, E. L. Thomas, and L. Kockel. 2010. With TOR, less is more: a key role for the conserved nutrientsensing TOR pathway in aging. Cell Metab. 11: 453-465
11. Meijer, A. J., and P. Codogno. 2008. Nutrient sens ing: TOR's Ragtime. Nat. Cell Biol. 10: 881-883
12. Sengupta, S., T. R. Peterson, and D. M. Sabatini. 2010. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol. Cell 40: 310-322.
13. Inaba K.,M. Inaba,M. Deguchi,K. Hagi,R. Yasumizu,S. Ikehara,S. Muramatsu,R.M. Steinman, 1993, Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class IInegative progenitor in mouse bone marrow, Proc. Natl. Acad. Sci. USA, 90, 3038-3042.
14. Jin, H. K., S. H. Ahn, J. W. Yoon, J. W. Park, E. K. Lee, J. S. Yoo, J. C. Lee, W. S. Choi, and J. W. Han. 2009. Rapamycin down-regulates inducible nitric oxide synthase by inducing proteasomal degradation. Biol. Pharm. Bull. 32: 988-992
15. Lisi, L., P. Navarra, D. L. Feinstein, and C. Dello Russo. 2011. The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes. J. Neuroinflammation 8: 1-11
16. Lu, D. Y., H. C. Liou, C. H. Tang, and W. M. Fu. 2006. Hypoxia-induced iNOS expression in microglia is regulated by the PI3-kinase/Akt/mTOR signaling pathway and activation of hypoxia inducible factor-1a. Biochem. Pharmacol. 72: 992-1000
17. Bran d, M. D., and D. G. Nicholls. 2011. Assessing mitochondrial dysfunction in cells. Biochem. J. 435: 297-312
18. Bian, S., X. Sun, A. Bai, C. Zhang, L. Li, K. Enjyoji, W. G. Junger, S. C. Robson, and Y. Wu. 2013. P2X7 integrates PI3K/AKT and AMPK-PRAS40-mTOR signaling pathways to mediate tumor cell death. PLoS ONE 8: e60184
19. Lee, J., S. Giordano, and J. Zhang. 2012. A utophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem. J. 441: 523-540
20. Bustamente, E., H. P. Morris, and P. L. Pedersen. 1977. Hexokinase: the direct link between mitochondrial and glycolytic reactions in rapidly growing cancer cells. Adv. Exp. Med. Biol. 92: 363-380
21. Chang, C. H., J. D. Curtis, L. B. Maggi, Jr., B. Faubert, A. V. Villarino, D. O'Sullivan, S. C. Huang, G. J. van der Windt, J. Blagih, J. Qiu, et al. 2013. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153: 1239-1251
22. Le Goffe, C., G. Vallette, A. Jarry, C. Bou-Hanna, and C. L. Laboisse. 1999. The in vitro manipulation of carbohydrate metabolism: a new strategy for deciphering the cellular defenc e mechanisms against nitric oxide attack. Biochem. J. 344: 643-648
23. Matés, J. M., J. A. Segura, J. A. Campos-Sandoval, C. Lobo, L. Alonso, F. J. Alonso, and J. Márquez. 2009. Glutamine homeostasis and mitochondrial dynamics. Int. J. Biochem. Cell Biol. 41: 2051-2061
24. Vats, D., L. Mukundan, J. I. Odegaard, L. Zhang, K. L. Smith, C. R. Morel, R. A. Wagner, D. R. Greaves, P. J. Murray, and A. Chawla. 2006. Oxidative metabolism and PGC-1b attenuate macrophage-mediated inflammation. Cell Metab. 4: 13-24
25. Gao, Y. 2010. The multiple actions of NO. Pflugers Arch. 459: 829-839
26. Wink, D. A., H. B. Hines, R. Y. Cheng, C. H. Switzer, W. Flores-Santana, M. P. Vitek, L. A. Ridnour, and C. A. Colton. 2011. Nitric oxide and redox mechanisms in the immune response. J. Leukoc. Biol. 89: 873-891
27. Adler, H. S., A. Simon, E. Graulich, A. Habermeier, N. Bacher, A. Friebe, E. I. Closs, and K. Steinbrink. 2010. Neuronal nitric oxide synthase modulates maturation of human dendritic cells. J. Immunol. 184: 6025-6034
28. Hoffman, R. A., R. S. Mahidhara, A. S. Wolf-Johnston, L. Lu, A. W. Thomson, and R. L. Simmons. 2002. Differential modulation of CD4 and CD8 T-cell proliferation by induction of nitric oxide synthesis in antigen presenting cells. Transplantation 74: 836-845
29. Serbina, N. V., W. Kuzie l, R. Flavell, S. Akira, B. Rollins, and E. G. Pamer. 2003. Sequential MyD88-independent and-dependent activation of innate immune responses to intracellular bacterial infection. Immunity 19: 891-901
30. Serbina, N. V., T. P. Salazar-Mather, C. A. Biron, W. A. Kuziel, and E. G. Pamer. 2003. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19: 59-70
31. Sugita, K., K. Kabashima, R. Yoshiki, A. Ikenouchi-Sugita, M. Tsutsui, J. Nakamura, N. Yanagihara, and Y. Tokura. 2010. Inducible nitric oxide synthase downmodulates contact hypersensitivity by suppressing dendritic cell migration and survival. J. Invest. Dermatol. 130: 464-471
32. Beltrá n, B., A. Mathur, M. R. Duchen, J. D. Erusalimsky, and S. Moncada. 2000. The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death. Proc. Natl. Acad. Sci. USA 97: 14602-14607
33. Cleeter, M. W., J. M. Cooper, V. M. Darley-Usmar, S. Moncada, and A. H. Schapira. 1994. Reversible inhibition of cytochrome c oxidase, the ter-minal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett. 345: 50-54.
34. Clementi E.,G. C. Brown,M. Feelisch,S. Moncada, 1998, Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathion e. Proc. Natl. Acad. Sci. USA, 95, 7631-7636.
35. Chou, Y. Y., J. I. Gao, S. F. Chang, P. Y. Chang, and S. C. Lu. 2011. Rapamycin inhibits lipopolysaccharide induction of granulocyte-colony stimul ating factor and inducible nitric oxide synthase expression in macrophages by reducing the levels of octamer-binding factor-2. FEBS J. 278: 85-96
36. Hackstein, H., T. Taner, A. F. Zahorchak, A. E. Morelli, A. J. Logar, A. Gessner, and A. W. Thomson. 2003. Rapamycin inhibits IL-4-induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood 101: 4457-4463
37. Sathaliyawala, T., W. E. O'Gorman, M. Greter, M. Bogunovic, V. Konjufca, Z. E. Hou, G. P. Nolan, M. J. Miller, M. Merad, and B. Reizis. 2010. Mammalian target of rapamycin controls dendritic cell development d ownstream of Flt3 ligand signaling. Immunity 33: 597-606
38. Woltman, A. M., S. W. van der Kooij, P. J. Coffer, R. Offringa, M. R. Daha, and C. van Kooten. 2003. Rapamycin specifically interf eres with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expression. Blood 101: 1439-1445
39. Haidinger, M., M. Poglitsch, R. Geyeregger, S. Kasturi, M. Zeyda, G. J. Zlabinger, B. Pulendran, W. H. Hörl, M. D. Säemann, and T. Weichhart. 2010. A versatile role of mammalian target of rapamycin in human dendritic cell function and differentiation. J. Immunol. 185: 3919-3931.
40. Weichhart, T., G. Costantino, M. Poglitsch, M. Rosner, M. Zeyda, K. M. Stuhlmeier, T. Kolbe, T. M. Stulnig, W. H. Hörl, M. Hengstschlä ger, et al. 2008. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29: 565-577
41. Weichhart, T., and M. D. Sä emann. 2009. The multiple facets of mTOR in immunity. Trends Immunol. 30: 218-226
42. Rastogi, R., Z. Jiang, N. Ahmad, R. Rosati, Y. Liu, L. Beuret, R. Monks, J. Charron, M. J. Birnbaum, and L. Samavati. 2013. Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 ( MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways. J. Biol. Chem. 288: 33966-33977
43. Leunda-Casi, A., G. Genicot, I. Donnay, S. Pampfer, and R . De Hertogh. 2002. Increased cell death in mouse blastocysts exposed to high D-glucose in vitro: implications of an oxidative stress and alterations in glucose metabolism. Diabetologia 45: 571-579
44. MacF arlane, M., G. L. Robinson, and K. Cain. 2012. Glucose-A sweet way to die: metabolic switching modulates tumor cell death. Cell Cycle 11: 3919-3925
45. Madan, E., R. Gogna, M. Bhatt, U. Pati, P. Kuppusamy, and A. A. Mahdi. 2011. Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor. Oncotarget 2: 948-957
46. Maddocks, O. D., and K. H. Vousden. 2011. Metabolic regulation by p53. J. Mol. Med. 89: 237-245
47. Robinson, G. L., D. Dinsdale, M. Macfarlane, and K. Cain. 2012. Switching from aerobic glycolysis to oxidative phosphorylation modulates the sensitivity of mantle cell lymphoma cells to TRAIL. Oncogene 31: 4996-5006
48. Shim, H., Y. S. Chun, B. C. Lewis, and C. V. Dang. 1998. A unique glucosedependent apoptotic pathway induced by c-Myc. Proc. Natl. Acad. Sci. USA 95: 1511-1516
49. Vander Heiden, M. G., D. R. Plas, J. C. Rathmell, C. J. Fox, M. H. Harris, and C. B. Thompson. 2001. Growth factors can influence cell growth and survival through effects on glucose metabolism. Mol. Cell. Biol. 21: 5899-5912
50. Araki, K., A. P. Turner, V. O. Shaffer, S. Gangappa, S. A. Keller, M. F. Bachmann, C. P. Larsen, and R. Ahmed. 2009. mTOR regulates memory CD8 T-cell differentiation. Nature 460: 108-112
51. Drake, C. G. 2011. Update on prostate cancer vaccines. Cancer J. 17: 294-299
52. Pearce, E. L., M. C. Walsh, P. J. Cejas, G. M. Harms, H. Shen, L. S. Wang, R. G. Jones, and Y. Choi. 2009. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460: 103-107
53. Rodrí guez-Prados, J. C., P. G. Través, J. Cuenca, D. Rico, J. Aragonés, P. Martín-Sanz, M. Cascante, and L. Boscá. 2010. Substrate fate in activa ted macrophages: a comparison between innate, classic, and alternative activation. J. Immunol. 185: 605-614
54. van der Windt, G. J., B. Everts, C. H. Chang, J. D. Curtis, T. C. Freitas, E. Amiel, E. J. Pearce, and E. L. Pearce. 2012. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36: 68-78.
55. Odegaard J.I.,A. Chawla, 2013, The immune system as a sensor of the metabolic state, Immunity, 38, 644-654.
56. Pearce, E. L., and E. J. Pearce. 2013. Metabolic pathways in immune cell activation and quiescence. Immunity 38: 633-643.
57. Jenny, N. S. 2012. Inflammation in aging: cause, effect, or both? Discov. Med. 13: 451-460