Mitochondrial Exhaustion of Memory CD4 T-Cells in Treated HIV-1 Infection-Immunometabolism-CSCIED科技核心评价数据库-手机版

Mitochondrial Exhaustion of Memory CD4 T-Cells in Treated HIV-1 Infection

Mitochondrial Exhaustion of Memory CD4 T-Cells in Treated HIV-1 Infection

ES评分 0 浏览量：604 下载量：0

DOI	10.20900/immunometab20220013
刊名	Immunometabolism IJ
年，卷(期)	2022, 4(2)
作者	Younes, Souheil-Antoine,
作者单位	[Younes, Souheil-Antoine] Emory Univ, Sch Med, Dept Pathol, Pathol Adv Translat Res PATRU, Atlanta, GA 30322 USA
摘要	People living with HIV (PLWH) who are immune non-responders (INR) to therapy are unable to restore their CD4 T-cell count and remain at great risk of morbidity and mortality. Here the mitochondrial defects that characterize memory CD4 T-cells in INR and causes of this mitochondrial exhaustion are reviewed. This review also describes the various reagents used to induce the expression of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha), the master regulator of mitochondrial biogenesis, which can restore mitochondria fitness and CD4 T-cell proliferation in INR. Due to sustained heightened inflammation in INR, the mitochondrial network is unable to be rejuvenated and requires attenuation of mediators of inflammation to rescue mitochondria and CD4 T-cell counts in INR.
Abstract	People living with HIV (PLWH) who are immune non-responders (INR) to therapy are unable to restore their CD4 T-cell count and remain at great risk of morbidity and mortality. Here the mitochondrial defects that characterize memory CD4 T-cells in INR and causes of this mitochondrial exhaustion are reviewed. This review also describes the various reagents used to induce the expression of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha), the master regulator of mitochondrial biogenesis, which can restore mitochondria fitness and CD4 T-cell proliferation in INR. Due to sustained heightened inflammation in INR, the mitochondrial network is unable to be rejuvenated and requires attenuation of mediators of inflammation to rescue mitochondria and CD4 T-cell counts in INR.
关键词	mitochondria; exhaustion; CD4 T-cells; pgc1 alpha
KeyWord	mitochondria; exhaustion; CD4 T-cells; pgc1 alpha
基金项目
页码	1-13

参考文献
相关文献

1. Lederman MM, Calabrese L, Funderburg NT, Clagett B, Medvik K, Bonilla H, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011;204(8):1217-26.
2. Piconi S, Trabattoni D, Gori A, Parisotto S, Magni C, Meraviglia P, et al. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4(+) T-cell counts during antiretroviral therapy. Aids. 2010;24(13):1991-2000.
3. Baker JV, Peng G, Rapkin J, Abrams DI, Silverberg MJ, MacArthur RD, et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS. 2008;22(7):841-8.
4. Lewden C, Chene G, Morlat P, Raffi F, Dupon M, Dellamonica P, et al. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr. 2007;46(1):72-7.
5. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365-71.
6. Jiang W, Lederman MM, Hunt P, Sieg SF, Haley K, Rodriguez B, et al. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis. 2009;199(8):1177-85.
7. Younes SA, Talla A, Pereira Ribeiro S, Saidakova EV, Korolevskaya LB, Shmagel KV, et al. Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction. J Clin Invest. 2018;128(11):5083-94.
8. Ferrari B, Da Silva AC, Liu KH, Saidakova EV, Korolevskaya LB, Shmagel KV, et al. Gut-derived bacterial toxins impair memory CD4 T-cell mitochondrialfunction in HIV-1infection. J Clin Invest. 2022 Mar 22;e149571. doi: 10.1172/JCI149571
9. Williams MA, Bevan MJ. Effector and memory CTL differentiation. Annu Rev Immunol. 2007;25:171-92.
10. Geltink RIK, Kyle RL, Pearce EL. Unraveling the Complex Interplay Between T Cell Metabolism and Function. Annu Rev Immunol. 2018;36:461-88.
11. OʼSullivan D. The metabolic spectrum of memory T cells. Immunol Cell Biol. 2019;97(7):636-46.
12. Wherry EJ, Ahmed R. Memory CD8 T-cell differentiation during viral infection. J Virol. 2004;78(11):5535-45.
13. Douek D. HIV disease progression: immune activation, microbes, and a leaky gut. Top HIV Med. 2007;15(4):114-7.
14. Kominsky DJ, Campbell EL, Colgan SP. Metabolic shifts in immunity and inflammation. J Immunol. 2010;184(8):4062-8.
15. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682-7.
16. Trautmann L, Said EA, Halwani R, Janbazian L, Chomont N, El-Far M, et al. Programmed death 1: a critical regulator of T-cell function and a strong target for immunotherapies for chronic viral infections. Current opinion in HIV and AIDS. 2007;2(3):219-27.
17. Patsoukis N, Sari D, Boussiotis VA. PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A. Cell Cycle. 2012;11(23):4305-9.
18. Sumida TS, Dulberg S, Schupp JC, Lincoln MR, Stillwell HA, Axisa PP, et al. Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells. Nat Immunol. 2022;23:632-42.
19. McNab F, Mayer-Barber K, Sher A, Wack A, OʼGarra A. Type I interferons in infectious disease. Nat Rev Immunol. 2015;15(2):87-103.
20. Bengsch B, Johnson AL, Kurachi M, Odorizzi PM, Pauken KE, Attanasio J, et al. Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion. Immunity. 2016;45(2):358-73.
21. Pino M, Pereira Ribeiro S, Pagliuzza A, Ghneim K, Khan A, Ryan E, et al. Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART. PLoS Pathog. 2021;17(8):e1009825.
22. Shive CL, Freeman ML, Younes SA, Kowal CM, Canaday DH, Rodriguez B, et al. Markers of T Cell Exhaustion and Senescence and Their Relationship to Plasma TGF-beta Levels in Treated HIV+ Immune Non-responders. Front Immunol. 2021;12:638010.
23. Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N. Regulatory T Cells and Human Disease. Annu Rev Immunol. 2020;38:541-66.
24. Wong HS, Park K, Gola A, Baptista AP, Miller CH, Deep D, et al. A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells. Cell. 2021;184(15):3981-97.e22.
25. Hu W, Wang ZM, Feng Y, Schizas M, Hoyos BE, van der Veeken J, et al. Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity. Nat Immunol. 2021;22(9):1163-74.
26. Campbell C, McKenney PT, Konstantinovsky D, Isaeva OI, Schizas M, Verter J, et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020;581(7809):475-9.
27. Dion ML, Poulin JF, Bordi R, Sylvestre M, Corsini R, Kettaf N, et al. HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity. 2004;21(6):757-68.
28. Furler RL, Newcombe KL, Del Rio Estrada PM, Reyes-Teran G, Uittenbogaart CH, Nixon DF. Histoarchitectural Deterioration of Lymphoid Tissues in HIV-1 Infection and in Aging. AIDS Res Hum Retroviruses. 2019;35(11-12):1148-59.
29. Zhao J, Schank M, Wang L, Li Z, Nguyen LN, Dang X, et al. Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV. Front Immunol. 2021;12:658420.
30. Vlasova VV, Saidakova EV, Korolevskaya LB, Shmagel NG, Chereshnev VA, Shmagel KV. Metabolic Features of Activated Memory CD4(+) T-Cells Derived from HIV-Infected Immunological Non-responders to Highly Active Antiretroviral Therapy. Dokl Biol Sci. 2021;501(1):206-9.
31. Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200(6):749-59.
32. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature. 2005;434(7037):1093-7.
33. Kleinman AJ, Sivanandham R, Pandrea I, Chougnet CA, Apetrei C. Regulatory T Cells As Potential Targets for HIV Cure Research. Front Immunol. 2018;9:734.
34. Vukmanovic-Stejic M, Zhang Y, Cook JE, Fletcher JM, McQuaid A, Masters JE, et al. Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest. 2006;116(9):2423-33.
35. Booth NJ, McQuaid AJ, Sobande T, Kissane S, Agius E, Jackson SE, et al. Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO. J Immunol. 2010;184(8):4317-26.
36. Younes SA, Punkosdy G, Caucheteux S, Chen T, Grossman Z, Paul WE. Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells. PLoS Biol. 2011;9(10):e1001171.
37. Roncarolo MG, Gregori S. Is FOXP3 a bona fide marker for human regulatory T cells? Eur J Immunol. 2008;38(4):925-7.
38. Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J Clin Invest. 2003;112(9):1437-43.
39. Allan SE, Passerini L, Bacchetta R, Crellin N, Dai M, Orban PC, et al. The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J Clin Invest. 2005;115(11):3276-84.
40. Paul WE, Milner JD, Grossman Z. Pathogen-sensing, regulatory T cells, and responsiveness-tuning collectively regulate foreign- and self-antigen mediated T-cell responses. Cold Spring Harb Symp Quant Biol. 2013;78:265-76.
41. Pandiyan P, Younes SA, Ribeiro SP, Talla A, McDonald D, Bhaskaran N, et al. Mucosal Regulatory T Cells and T Helper 17 Cells in HIV-Associated Immune Activation. Front Immunol. 2016;7:228.
42. de Jong SE, Olin A, Pulendran B. The Impact of the Microbiome on Immunity to Vaccination in Humans. Cell Host Microbe. 2020;28(2):169-79.
43. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55-71.
44. Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 2014;7(4):983-94.
45. Dinh DM, Volpe GE, Duffalo C, Bhalchandra S, Tai AK, Kane AV, et al. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J Infect Dis. 2015;211(1):19-27.
46. Mutlu EA, Keshavarzian A, Losurdo J, Swanson G, Siewe B, Forsyth C, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 2014;10(2):e1003829.
47. Nganou-Makamdop K, Talla A, Sharma AA, Darko S, Ransier A, Laboune F, et al. Translocated microbiome composition determines immunological outcome in treated HIV infection. Cell. 2021;184(15):3899-914.e16.
48. Han H, Zhu J, Zhu Z, Ni J, Du R, Dai Y, et al. p-Cresyl sulfate aggravates cardiac dysfunction associated with chronic kidney disease by enhancing apoptosis of cardiomyocytes. J Am Heart Assoc. 2015;4(6):e001852.
49. Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel). 2017 Jan 29;9(2):52. doi: 10.3390/toxins9020052
50. Watanabe H, Miyamoto Y, Honda D, Tanaka H, Wu Q, Endo M, et al. p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int. 2013;83(4):582-92.
51. Mair RD, Sirich TL, Meyer TW. Uremic Toxin Clearance and Cardiovascular Toxicities. Toxins (Basel). 2018 Jun 2;10(6):226. doi: 10.3390/toxins10060226
52. Fisicaro P, Barili V, Montanini B, Acerbi G, Ferracin M, Guerrieri F, et al. Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B. Nat Med. 2017;23(3):327-36.
53. Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, et al. The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction. Immunity. 2016;45(3):701-3.
54. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2010;47:69-84.
55. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109-22.
56. Visnjic D, Lalic H, Dembitz V, Tomic B, Smoljo T. AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review. Cells. 2021 May 4;10(5):1095. doi: 10.3390/cells10051095
57. Lei J, Hasegawa H, Matsumoto T, Yasukawa M. Peroxisome proliferator-activated receptor alpha and gamma agonists together with TGF-beta convert human CD4+CD25− T cells into functional Foxp3+ regulatory T cells. J Immunol. 2010;185(12):7186-98.
58. Komen JC, Thorburn DR. Turn up the power -pharmacological activation of mitochondrial biogenesis in mouse models. Br J Pharmacol. 2014;171(8):1818-36.
59. Beier U, Angelin A, Jiao J, Xiao H, Wang L, Dahiya S, et al. Foxp3 Controls Oxidative Phosphorylation in Regulatory T Cells. Am J Transplant. 2016;16:291.
60. Marson A, Kretschmer K, Frampton GM, Jacobsen ES, Polansky JK, MacIsaac KD, et al. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature. 2007;445(7130):931-5.
61. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330-6.
62. Morris SR, Chen B, Mudd JC, Panigrahi S, Shive CL, Sieg SF, et al. Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15. JCI Insight. 2020;5(11):e132963. doi: 10.1172/jci.insight.132963
63. Wang F, Meng M, Mo B, Yang Y, Ji Y, Huang P, et al. Crosstalks between mTORC1 and mTORC2 variagate cytokine signaling to control NK maturation and effector function. Nat Commun. 2018;9(1):4874.
64. Viel S, Besson L, Marotel M, Walzer T, Marcais A. Regulation of mTOR, Metabolic Fitness, and Effector Functions by Cytokines in Natural Killer Cells. Cancers (Basel). 2017 Sep 28;9(10):132. doi: 10.3390/cancers9100132
65. Liu Z, Liang G, Gui L, Li Y, Liu M, Bai Y, et al. Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice. Sci Rep. 2017;7(1):6028.
66. Mao Y, van Hoef V, Zhang X, Wennerberg E, Lorent J, Witt K, et al. IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells. Blood. 2016;128(11):1475-89.
67. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007;450(7170):736-40.
68. Adams WC, Chen YH, Kratchmarov R, Yen B, Nish SA, Lin WW, et al. Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal. Cell Rep. 2016;17(12):3142-52.
69. Sukumar M, Liu J, Mehta GU, Patel SJ, Roychoudhuri R, Crompton JG, et al. Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy. Cell Metab. 2016;23(1):63-76.
70. Katajisto P, Dohla J, Chaffer CL, Pentinmikko N, Marjanovic N, Iqbal S, et al. Stem cells. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science. 2015;348(6232):340-3.
71. Dohla J, Kuuluvainen E, Gebert N, Amaral A, Englund JI, Gopalakrishnan S, et al. Metabolic determination of cell fate through selective inheritance of mitochondria. Nat Cell Biol. 2022;24(2):148-54.
72. Vujkovic-Cvijin I, Rutishauser RL, Pao M, Hunt PW, Lynch SV, McCune JM, et al. Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals. Gut Microbes. 2017;8(5):440-50.
73. Serrano-Villar S, Talavera-Rodriguez A, Gosalbes MJ, Madrid N, Perez-Molina JA, Elliott RJ, et al. Fecal microbiota transplantation in HIV: A pilot placebo-controlled study. Nat Commun. 2021;12(1):1139.
74. d'Ettorre G, Ceccarelli G, Giustini N, Serafino S, Calantone N, De Girolamo G, et al. Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the “Probio-HIV” Clinical Trial. PLoS One. 2015;10(9):e0137200.
75. Presti RM, Yeh E, Williams B, Landay A, Jacobson JM, Wilson C, et al. A Randomized, Placebo-Controlled Trial Assessing the Effect of VISBIOME ES Probiotic in People With HIV on Antiretroviral Therapy. Open Forum Infect Dis. 2021;8(12):ofab550.
76. Geng ST, Zhang JB, Wang YX, Xu Y, Lu D, Zhang Z, et al. Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4(+) T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders. Front Immunol. 2021;12:757935.
77. Olalla J, Garcia de Lomas JM, Chueca N, Perez-Stachowski X, De Salazar A, Del Arco A, et al. Effect of daily consumption of extra virgin olive oil on the lipid profile and microbiota of HIV-infected patients over 50 years of age. Medicine (Baltimore). 2019;98(42):e17528.
78. Pastor-Ibanez R, Blanco-Heredia J, Etcheverry F, Sanchez-Palomino S, Diez-Fuertes F, Casas R, et al. Adherence to a Supplemented Mediterranean Diet Drives Changes in the Gut Microbiota of HIV-1-Infected Individuals. Nutrients. 2021 Mar 30;13(4):1141. doi: 10.3390/nu13041141

引用本文

Younes, Souheil-Antoine. Mitochondrial Exhaustion of Memory CD4 T-Cells in Treated HIV-1 Infection [J]. Immunometabolism. 2022; 4; (2). 1 - 13.

文献评论

相关学者

相关机构