Contribution of ROS and metabolic status to neonatal and adult CD8+ T cell activation


Autoři: José Antonio Sánchez-Villanueva aff001;  Otoniel Rodríguez-Jorge aff001;  Oscar Ramírez-Pliego aff001;  Gabriela Rosas Salgado aff002;  Wassim Abou-Jaoudé aff003;  Céline Hernandez aff003;  Aurélien Naldi aff003;  Denis Thieffry aff003;  María Angélica Santana aff001
Působiště autorů: Centro de Investigación en Dinámica Celular (IICBA), Universidad Autónoma del Estado de Morelos (UAEM), Cuernavaca, Morelos, México aff001;  Facultad de Medicina, Universidad Autónoma del Estado de Morelos (UAEM), Cuernavaca, Morelos, México aff002;  Département de Biologie, Institut de Biologie de l’École Normale Supérieure (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226388

Souhrn

In neonatal T cells, a low response to infection contributes to a high incidence of morbidity and mortality of neonates. Here we have evaluated the impact of the cytoplasmic and mitochondrial levels of Reactive Oxygen Species of adult and neonatal CD8+ T cells on their activation potential. We have also constructed a logical model connecting metabolism and ROS with T cell signaling. Our model indicates the interplay between antigen recognition, ROS and metabolic status in T cell responses. This model displays alternative stable states corresponding to different cell fates, i.e. quiescent, activated and anergic states, depending on ROS levels. Stochastic simulations with this model further indicate that differences in ROS status at the cell population level contribute to the lower activation rate of neonatal, compared to adult, CD8+ T cells upon TCR engagement. These results are relevant for neonatal health care. Our model can serve to analyze the impact of metabolic shift during cancer in which, similar to neonatal cells, a high glycolytic rate and low concentrations of glutamine and arginine promote tumor tolerance.

Klíčová slova:

Cell metabolism – Cytotoxic T cells – Glutamine – Mitochondria – Neonates – T cells – Redox signaling – Anergy


Zdroje

1. PrabhuDas M, Adkins B, Gans H, King C, Levy O, Ramilo O, et al. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. 2011;12(3):189–94. Epub 2011/02/16. doi: 10.1038/ni0311-189 21321588.

2. Adkins B. Neonatal T cell function. J Pediatr Gastroenterol Nutr. 2005;40 Suppl 1:S5–7. Epub 2005/04/05. doi: 10.1097/00005176-200504001-00004 15805855.

3. Fike AJ, Kumova OK, Carey AJ. Dissecting the defects in the neonatal CD8(+) T-cell response. J Leukoc Biol. 2019. Epub 2019/07/02. doi: 10.1002/JLB.5RU0319-105R 31260598.

4. Marchant A, Goldman M. T cell-mediated immune responses in human newborns: ready to learn? Clin Exp Immunol. 2005;141(1):10–8. Epub 2005/06/17. doi: 10.1111/j.1365-2249.2005.02799.x 15958064; PubMed Central PMCID: PMC1809424.

5. Ndure J, Flanagan KL. Targeting regulatory T cells to improve vaccine immunogenicity in early life. Front Microbiol. 2014;5:477. Epub 2014/10/14. doi: 10.3389/fmicb.2014.00477 25309517; PubMed Central PMCID: PMC4161046.

6. Hasko G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends Immunol. 2004;25(1):33–9. Epub 2003/12/31. doi: 10.1016/j.it.2003.11.003 14698282.

7. Levy O, Coughlin M, Cronstein BN, Roy RM, Desai A, Wessels MR. The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J Immunol. 2006;177(3):1956–66. Epub 2006/07/20. doi: 10.4049/jimmunol.177.3.1956 16849509; PubMed Central PMCID: PMC2881468.

8. Elahi S. New insight into an old concept: role of immature erythroid cells in immune pathogenesis of neonatal infection. Front Immunol. 2014;5:376. Epub 2014/08/28. doi: 10.3389/fimmu.2014.00376 25161654; PubMed Central PMCID: PMC4129624.

9. Chatterton DE, Nguyen DN, Bering SB, Sangild PT. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int J Biochem Cell Biol. 2013;45(8):1730–47. Epub 2013/05/11. doi: 10.1016/j.biocel.2013.04.028 23660296.

10. Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007;7(5):379–90. Epub 2007/04/26. doi: 10.1038/nri2075 17457344.

11. Liu CY, Wang YM, Wang CL, Feng PH, Ko HW, Liu YH, et al. Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14(-)/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol. 2010;136(1):35–45. Epub 2009/07/03. doi: 10.1007/s00432-009-0634-0 19572148.

12. Monticelli LA, Buck MD, Flamar AL, Saenz SA, Tait Wojno ED, Yudanin NA, et al. Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation. Nat Immunol. 2016;17(6):656–65. Epub 2016/04/05. doi: 10.1038/ni.3421 27043409; PubMed Central PMCID: PMC4873382.

13. Vaupel P, Multhoff G. Commentary: A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment. Front Immunol. 2016;7:332. Epub 2016/09/16. doi: 10.3389/fimmu.2016.00332 27629240; PubMed Central PMCID: PMC5006596.

14. Wang Z, Shi X, Li Y, Fan J, Zeng X, Xian Z, et al. Blocking autophagy enhanced cytotoxicity induced by recombinant human arginase in triple-negative breast cancer cells. Cell Death Dis. 2014;5:e1563. Epub 2014/12/17. doi: 10.1038/cddis.2014.503 25501824; PubMed Central PMCID: PMC4454157.

15. Lemos H, Huang L, Prendergast GC, Mellor AL. Immune control by amino acid catabolism during tumorigenesis and therapy. Nat Rev Cancer. 2019;19(3):162–75. Epub 2019/01/31. doi: 10.1038/s41568-019-0106-z 30696923.

16. Szefel J, Danielak A, Kruszewski WJ. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv Med Sci. 2019;64(1):104–10. Epub 2019/01/04. doi: 10.1016/j.advms.2018.08.018 30605863.

17. Wu WC, Sun HW, Chen J, OuYang HY, Yu XJ, Chen HT, et al. Immunosuppressive immature myeloid cell generation is controlled by glutamine metabolism in human cancer. Cancer Immunol Res. 2019. Epub 2019/08/08. doi: 10.1158/2326-6066.CIR-18-0902 31387898.

18. Galindo-Albarran AO, Lopez-Portales OH, Gutierrez-Reyna DY, Rodriguez-Jorge O, Sanchez-Villanueva JA, Ramirez-Pliego O, et al. CD8(+) T Cells from Human Neonates Are Biased toward an Innate Immune Response. Cell Rep. 2016;17(8):2151–60. Epub 2016/11/17. doi: 10.1016/j.celrep.2016.10.056 27851975.

19. Meszaros G, Orban C, Kaposi A, Toldi G, Gyarmati B, Tulassay T, et al. Altered mitochondrial response to activation of T-cells in neonate. Acta Physiol Hung. 2015;102(2):216–27. Epub 2015/06/24. doi: 10.1556/036.102.2015.2.12 26100311.

20. Palin AC, Ramachandran V, Acharya S, Lewis DB. Human neonatal naive CD4+ T cells have enhanced activation-dependent signaling regulated by the microRNA miR-181a. J Immunol. 2013;190(6):2682–91. Epub 2013/02/15. doi: 10.4049/jimmunol.1202534 23408835; PubMed Central PMCID: PMC3952015.

21. Toldi G, Treszl A, Pongor V, Gyarmati B, Tulassay T, Vasarhelyi B. T-lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in the neonate. Int Immunol. 2010;22(9):769–74. Epub 2010/07/06. doi: 10.1093/intimm/dxq063 20601376.

22. Milkovic L, Cipak Gasparovic A., Mouthuy P.A., Zarkovic N. Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts. Cells. 2019;8(8):14. Epub July 30 2019. doi: 10.3390/cells8080793 31366062

23. Weinberg F, Ramnath N, Nagrath D. Reactive Oxygen Species in the Tumor Microenvironment: An Overview. Cancers (Basel). 2019;11(8). Epub 2019/08/21. doi: 10.3390/cancers11081191 31426364.

24. Naldi A, Hernandez C, Abou-Jaoude W, Monteiro PT, Chaouiya C, Thieffry D. Logical Modeling and Analysis of Cellular Regulatory Networks With GINsim 3.0. Front Physiol. 2018;9:646. doi: 10.3389/fphys.2018.00646 29971008; PubMed Central PMCID: PMC6018412.

25. Hernandez-Acevedo GN, Lopez-Portales OH, Gutierrez-Reyna DY, Cuevas-Fernandez E, Kempis-Calanis LA, Labastida-Conde RG, et al. Protein complexes associated with beta-catenin differentially influence the differentiation profile of neonatal and adult CD8(+) T cells. J Cell Physiol. 2019;234(10):18639–52. Epub 2019/03/30. doi: 10.1002/jcp.28502 30924167.

26. Stoll G, Caron B, Viara E, Dugourd A, Zinovyev A, Naldi A, et al. MaBoSS 2.0: an environment for stochastic Boolean modeling. Bioinformatics. 2017;33(14):2226–8. doi: 10.1093/bioinformatics/btx123 28881959.

27. Stoll G, Viara E, Barillot E, Calzone L. Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm. BMC Syst Biol. 2012;6:116. doi: 10.1186/1752-0509-6-116 22932419; PubMed Central PMCID: PMC3517402.

28. Naldi A, Hernandez C, Levy N, Stoll G, Monteiro PT, Chaouiya C, et al. The CoLoMoTo Interactive Notebook: Accessible and Reproducible Computational Analyses for Qualitative Biological Networks. Front Physiol. 2018;9:680. doi: 10.3389/fphys.2018.00680 29971009; PubMed Central PMCID: PMC6018415.

29. Li Y, Jia A, Wang Y, Dong L, Wang Y, He Y, et al. Immune effects of glycolysis or oxidative phosphorylation metabolic pathway in protecting against bacterial infection. J Cell Physiol. 2019;234(11):20298–309. doi: 10.1002/jcp.28630 30972784.

30. Previte DM, O'Connor EC, Novak EA, Martins CP, Mollen KP, Piganelli JD. Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation. PLoS One. 2017;12(4):e0175549. doi: 10.1371/journal.pone.0175549 28426686; PubMed Central PMCID: PMC5398529.

31. Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, et al. Glutathione Primes T Cell Metabolism for Inflammation. Immunity. 2017;46(6):1089–90. doi: 10.1016/j.immuni.2017.06.009 28636957.

32. Medzhitov R. Bringing Warburg to lymphocytes. Nat Rev Immunol. 2015;15(10):598. Epub 2015/09/26. doi: 10.1038/nri3918 26403193.

33. Asuaje A, Smaldini P, Martin P, Enrique N, Orlowski A, Aiello EA, et al. The inhibition of voltage-gated H(+) channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis. Pflugers Arch. 2017;469(2):251–61. doi: 10.1007/s00424-016-1928-0 28013412.

34. Rodriguez-Jorge O, Kempis-Calanis LA, Abou-Jaoude W, Gutierrez-Reyna DY, Hernandez C, Ramirez-Pliego O, et al. Cooperation between T cell receptor and Toll-like receptor 5 signaling for CD4(+) T cell activation. Sci Signal. 2019;12(577). Epub 2019/04/18. doi: 10.1126/scisignal.aar3641 30992399.

35. Simeoni L, Bogeski I. Redox regulation of T-cell receptor signaling. Biol Chem. 2015;396(5):555–68. doi: 10.1515/hsz-2014-0312 25781677.

36. Li-Weber M, Salgame P, Hu C, Davydov IV, Laur O, Klevenz S, et al. Th2-specific protein/DNA interactions at the proximal nuclear factor-AT site contribute to the functional activity of the human IL-4 promoter. J Immunol. 1998;161(3):1380–9. Epub 1998/08/01. 9686601.

37. Anupam K, Kaushal J, Prabhakar N, Bhatnagar A. Effect of redox status of peripheral blood on immune signature of circulating regulatory and cytotoxic T cells in streptozotocin induced rodent model of type I diabetes. Immunobiology. 2018;223(10):586–97. Epub 2018/07/19. doi: 10.1016/j.imbio.2018.07.004 30017263.

38. Seo YS, Kim HS, Lee AY, Chun JM, Kim SB, Moon BC, et al. Codonopsis lanceolata attenuates allergic lung inflammation by inhibiting Th2 cell activation and augmenting mitochondrial ROS dismutase (SOD2) expression. Sci Rep. 2019;9(1):2312. Epub 2019/02/21. doi: 10.1038/s41598-019-38782-6 30783201; PubMed Central PMCID: PMC6381190.

39. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1–13. doi: 10.1042/BJ20081386 19061483; PubMed Central PMCID: PMC2605959.

40. Patel B, Zheleznova NN, Ray SC, Sun J, Cowley AW Jr., O'Connor PM. Voltage gated proton channels modulate mitochondrial reactive oxygen species production by complex I in renal medullary thick ascending limb. Redox Biol. 2019:101191. doi: 10.1016/j.redox.2019.101191 31060879.

41. Rossi A, Pizzo P, Filadi R. Calcium, mitochondria and cell metabolism: A functional triangle in bioenergetics. Biochim Biophys Acta Mol Cell Res. 2019;1866(7):1068–78. doi: 10.1016/j.bbamcr.2018.10.016 30982525.

42. Elahi S, Ertelt JM, Kinder JM, Jiang TT, Zhang X, Xin L, et al. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection. Nature. 2013;504(7478):158–62. doi: 10.1038/nature12675 24196717; PubMed Central PMCID: PMC3979598.

43. den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mogling R, de Boer AB, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012;36(2):288–97. Epub 2012/03/01. doi: 10.1016/j.immuni.2012.02.006 22365666.


Článek vyšel v časopise

PLOS One


2019 Číslo 12