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Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis


Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication ofM. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation.

Keywords:
Tuberculosis, Multidrug resistance, Host-directed therapies, Immunomodulatory agents, Immune response, Inflammation


Autoři: Alimuddin Zumla† 1;  Martin Rao† 2;  Ernest Dodoo 2;  Markus Maeurer† 2,3*
Působiště autorů: Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK. 1;  F79, Therapeutic Immunology (TIM) division, Department of Laboratory Medicine (LABMED), Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden. 2;  Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden. †Equal contributors 3
Vyšlo v časopise: BMC Medicine 2016, 14:89
Kategorie: Review
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12916-016-0635-1

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0635-1

Souhrn

Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication ofM. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation.

Keywords:
Tuberculosis, Multidrug resistance, Host-directed therapies, Immunomodulatory agents, Immune response, Inflammation


Zdroje

1. WHO. Global Tuberculosis Report 2015. Geneva: World Health Organization; 2015. p. 204.

2. Schnippel K, Rosen S, Shearer K, Martinson N, Long L, Sanne I, Variava E. Costs of inpatient treatment for multi-drug-resistant tuberculosis in South Africa. Trop Med Int Health. 2013;18(1):109–16.

3. Dheda K, Gumbo T, Gandhi NR, Murray M, Theron G, Udwadia Z, Migliori GB, Warren R. Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis. Lancet Respir Med. 2014;2(4):321–38.

4. Zumla A, Rao M, Parida SK, Keshavjee S, Cassell G, Wallis R, Axelsson-Robertsson R, Doherty M, Andersson J, Maeurer M. Inflammation and tuberculosis: host-directed therapies. J Intern Med. 2015;277(4):373–87.

5. Lai RP, Meintjes G, Wilkinson RJ. HIV-1 tuberculosis-associated immune reconstitution inflammatory syndrome. Semin Immunopathol. 2015. doi:10.1007/s00281-015-0532-2.

6. Ravimohan S, Tamuhla N, Steenhoff AP, Letlhogile R, Nfanyana K, Bellamy SL, MacGregor RR, Gross R, Weissman D, Bisson GP. Immunological profiling of tuberculosis-associated immune reconstitution inflammatory syndrome and non-immune reconstitution inflammatory syndrome death in HIV-infected adults with pulmonary tuberculosis starting antiretroviral therapy: a prospective observational cohort study. Lancet Infect Dis. 2015. doi:10.1016/S1473-3099(15)70008-3.

7. Zumla A, Rao M, Parida SK, Keshavjee S, Cassell G, Wallis R, Axelsson-Robertsson R, Doherty M, Andersson J, Maeurer M. Inflammation and tuberculosis: hostdirected therapies. J Intern Med. 2014. doi:10.1111/joim.12256.

8. Meintjes G, Rangaka MX, Maartens G, Rebe K, Morroni C, Pepper DJ, Wilkinson KA, Wilkinson RJ. Novel relationship between tuberculosis immune reconstitution inflammatory syndrome and antitubercular drug resistance. Clin Infect Dis. 2009;48(5):667–76.

9. Pasipanodya JG, McNabb SJ, Hilsenrath P, Bae S, Lykens K, Vecino E, Munguia G, Miller TL, Drewyer G, Weis SE. Pulmonary impairment after tuberculosis and its contribution to TB burden. BMC Public Health. 2010;10:259.

10. Zumla A, Chakaya J, Centis R, D'Ambrosio L, Mwaba P, Bates M, Kapata N, Nyirenda T, Chanda D, Mfinanga S, et al. Tuberculosis treatment and management–an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 2015;3(3):220–34.

11. Pinho ST, Rodrigues P, Andrade RF, Serra H, Lopes JS, Gomes MG. Impact of tuberculosis treatment length and adherence under different transmission intensities. Theor Popul Biol. 2015;104:68–77.

12. Hoger S, Lykens K, Beavers SF, Katz D, Miller TL. Longevity loss among cured tuberculosis patients and the potential value of prevention. Int J Tuberc Lung Dis. 2014;18(11):1347–52.

13. Kaufmann SH, Lange C, Rao M, Balaji KN, Lotze M, Schito M, Zumla AI, Maeurer M. Progress in tuberculosis vaccine development and host-directed therapies–a state of the art review. Lancet Respir Med. 2014;2(4):301–20.

14. Ahmed RK, Rohava Z, Balaji KN, Hoffner SE, Gaines H, Magalhaes I, Zumla A, Skrahina A, Maeurer MJ. Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus. BMC Infect Dis. 2012;12(1):41.

15. Berry MP, Graham CM, McNab FW, Xu Z, Bloch SA, Oni T, Wilkinson KA, Banchereau R, Skinner J, Wilkinson RJ, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 2010;466(7309):973–7.

16. Wallis RS, Kim P, Cole S, Hanna D, Andrade BB, Maeurer M, Schito M, Zumla A. Tuberculosis biomarkers discovery: developments, needs, and challenges. Lancet Infect Dis. 2013;13(4):362–72.

17. Zumla AI, Schito M, Maeurer M. Advancing the portfolio of tuberculosis diagnostics, drugs, biomarkers, and vaccines. Lancet Infect Dis. 2014; 14(4):267–9.

18. Mahon RN, Hafner R. Immune Cell Regulatory Pathways Unexplored as Host-Directed Therapeutic Targets for Mycobacterium tuberculosis: An Opportunity to Apply Precision Medicine Innovations to Infectious Diseases. Clin Infect Dis. 2015;61 suppl 3:S200–16.

19. Zumla A, Chakaya J, Hoelscher M, Ntoumi F, Rustomjee R, Vilaplana C, Yeboah-Manu D, Rasolof V, Munderi P, Singh N, et al. Towards host-directed therapies for tuberculosis. Nat Rev Drug Discov. 2015. doi:10.1038/nrd4696.

20. Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, Winzeler B, Bingisser R, Elsaesser H, Drozdov D, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015. doi:10.1016/S0140-6736(14)62447-8.

21. Remmelts HH, Meijvis SC, Biesma DH, van Velzen-Blad H, Voorn GP, Grutters JC, Bos WJ, Rijkers GT. Dexamethasone downregulates the systemic cytokine response in patients with community-acquired pneumonia. Clin Vaccine Immunol. 2012;19(9):1532–8.

22. Muthuswamy P, Hu TC, Carasso B, Antonio M, Dandamudi N. Prednisone as adjunctive therapy in the management of pulmonary tuberculosis. Report of 12 cases and review of the literature. Chest. 1995;107(6):1621–30.

23. Tobin DM, Ramakrishnan L. TB: the Yin and Yang of lipid mediators. Curr Opin Pharmacol. 2013;13(4):641–5.

24. Zelasko S, Arnold WR, Das A. Endocannabinoid metabolism by cytochrome P450 monooxygenases. Prostaglandins Other Lipid Mediat. 2014. doi:10.1016/j.prostaglandins.2014.11.002.

25. Agarwal S, Reddy GV, Reddanna P. Eicosanoids in inflammation and cancer: the role of COX-2. Expert Rev Clin Immunol. 2009;5(2):145–65.

26. Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell. 2012;148(3):434–46.

27. Vilaplana C, Marzo E, Tapia G, Diaz J, Garcia V, Cardona PJ. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J Infect Dis. 2013;208(2):199–202.

28. Guzman JD, Evangelopoulos D, Gupta A, Birchall K, Mwaigwisya S, Saxty B, McHugh TD, Gibbons S, Malkinson J, Bhakta S. Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HTSPOTi whole-cell phenotypic assay. BMJ Open. 2013;3(6). doi:10.1136/bmjopen-2013-002672.

29. Berger W, De Chandt MT, Cairns CB. Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease. Int J Clin Pract. 2007;61(4):663–76.

30. Mayer-Barber KD, Andrade BB, Oland SD, Amaral EP, Barber DL, Gonzales J, Derrick SC, Shi R, Kumar NP, Wei W, et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature. 2014;511(7507):99–103.

31. Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005;4(12):977–87.

32. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000;6(12):1399–402.

33. Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP, Sorensen HT. Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. Arch Intern Med. 2008;168(19):2081–7.

34. Thomsen RW, Hundborg HH, Johnsen SP, Pedersen L, Sorensen HT, Schonheyder HC, Lervang HH. Statin use and mortality within 180 days after bacteremia: a population-based cohort study. Crit Care Med. 2006;34(4):1080–6.

35. Chalmers JD, Singanayagam A, Murray MP, Hill AT. Prior statin use is associated with improved outcomes in community-acquired pneumonia. Am J Med. 2008;121(11):1002–7. e1001.

36. Mortensen EM, Restrepo MI, Anzueto A, Pugh J. The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir Res. 2005;6:82.

37. Parihar SP, Guler R, Khutlang R, Lang DM, Hurdayal R, Mhlanga MM, Suzuki H, Marais AD, Brombacher F. Statin therapy reduces the mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation. J Infect Dis. 2014;209(5):754–63.

38. Skerry C, Pinn ML, Bruiners N, Pine R, Gennaro ML, Karakousis PC. Simvastatin increases the in vivo activity of the first-line tuberculosis regimen. J Antimicrob Chemother. 2014;69(9):2453–7.

39. Kang YA, Choi NK, Seong JM, Heo EY, Koo BK, Hwang SS, Park BJ, Yim JJ, Lee CH. The effects of statin use on the development of tuberculosis among patients with diabetes mellitus. Int J Tuberc Lung Dis. 2014;18(6):717–24.

40. Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: From Mechanisms of Action to Therapies. Cell Metab. 2014;20(6):953–66.

41. Singhal A, Jie L, Kumar P, Hong GS, Leow MK, Paleja B, Tsenova L, Kurepina N, Chen J, Zolezzi F, et al. Metformin as adjunct antituberculosis therapy. Sci Transl Med. 2014;6(263):263ra159.

42. Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112(6):1809–14.

43. Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG, Choi Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009;460(7251):103–7.

44. Napier RJ, Norris BA, Swimm A, Giver CR, Harris WA, Laval J, Napier BA, Patel G, Crump R, Peng Z, et al. Low doses of imatinib induce myelopoiesis and enhance host anti-microbial immunity. PLoS Pathog. 2015;11(3):e1004770.

45. Napier RJ, Rafi W, Cheruvu M, Powell KR, Zaunbrecher MA, Bornmann W, Salgame P, Shinnick TM, Kalman D. Imatinib-sensitive tyrosine kinases regulate mycobacterial pathogenesis and represent therapeutic targets against tuberculosis. Cell Host Microbe. 2011;10(5):475–85.

46. Riches JC, Gribben JG. Immunomodulation and immune reconstitution in chronic lymphocytic leukemia. Semin Hematol. 2014;51(3):228–34.

47. Boddy AV, Yule SM. Metabolism and pharmacokinetics of oxazaphosphorines. Clin Pharmacokinet. 2000;38(4):291–304.

48. Hall AG, Tilby MJ. Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies. Blood Rev. 1992;6(3):163–73.

49. Dimeloe S, Frick C, Fischer M, Gubser PM, Razik L, Bantug GR, Ravon M, Langenkamp A, Hess C. Human regulatory T cells lack the cyclophosphamide extruding transporter ABCB1 and are more susceptible to cyclophosphamideinduced apoptosis. Eur J Immunol. 2014;44(12):3614–20.

50. Kanakry CG, Ganguly S, Zahurak M, Bolanos-Meade J, Thoburn C, Perkins B, Fuchs EJ, Jones RJ, Hess AD, Luznik L. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med. 2013;5(211):211ra157.

51. Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012;18(8):1254–61.

52. Zumla A, Maeurer M. Rational development of adjunct immune-based therapies for drug-resistant tuberculosis: hypotheses and experimental designs. J Infect Dis. 2012;205 Suppl 2:S335–339.

53. Li N, Xie WP, Kong H, Min R, Hu CM, Zhou XB, Lu ZM, Ji XH, Wang H. Enrichment of regulatory T-cells in blood of patients with multidrugresistant tuberculosis. Int J Tuberc Lung Dis. 2015;19(10):1230–8.

54. Singh A, Dey AB, Mohan A, Sharma PK, Mitra DK. Foxp3+ regulatory T cells among tuberculosis patients: impact on prognosis and restoration of antigen specific IFN-gamma producing T cells. PLoS One. 2012;7(9):e44728.

55. Marks PA, Richon VM, Miller T, Kelly WK. Histone deacetylase inhibitors. Adv Cancer Res. 2004;91:137–68.

56. Lane AA, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol. 2009;27(32):5459–68.

57. Hymes KB. The role of histone deacetylase inhibitors in the treatment of patients with cutaneous T-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010;10(2):98–109.

58. Duenas-Gonzalez A, Candelaria M, Perez-Plascencia C, Perez-Cardenas E, de la Cruz-Hernandez E, Herrera LA. Valproic acid as epigenetic cancer drug: preclinical, clinical and transcriptional effects on solid tumors. Cancer Treat Rev. 2008;34(3):206–22.

59. Cang S, Ma Y, Liu D. New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer. J Hematol Oncol. 2009;2:22.

60. Han BR, You BR, Park WH. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013. doi:10.3892/or.2013.2747.

61. Fu J, Shao CJ, Chen FR, Ng HK, Chen ZP. Autophagy induced by valproic acid is associated with oxidative stress in glioma cell lines. Neuro Oncol.

2010;12(4):328–40.

62. Campbell GR, Bruckman RS, Chu YL, Spector SA. Autophagy induction by histone deacetylase inhibitors inhibits HIV type 1. J Biol Chem. 2015; 290(8):5028–40.

63. Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM. Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. Aids. 2004;18(8):1101–8.

64. Archin NM, Keedy KS, Espeseth A, Dang H, Hazuda DJ, Margolis DM. Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. Aids. 2009;23(14):1799–806.

65. Yang HC, Xing S, Shan L, O'Connell K, Dinoso J, Shen A, Zhou Y, Shrum CK, Han Y, Liu JO, et al. Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest. 2009;119(11):3473–86.

66. Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012;36(3):491–501.

67. Rasmussen TA, Tolstrup M, Winckelmann A, Ostergaard L, Sogaard OS. Eliminating the latent HIV reservoir by reactivation strategies: Advancing to clinical trials. Hum Vaccin Immunother. 2013;9(4):790–9.

68. Shirakawa K, Chavez L, Hakre S, Calvanese V, Verdin E. Reactivation of latent HIV by histone deacetylase inhibitors. Trends Microbiol. 2013;21(6):277–85.

69. Nelson J, Roe K, Orillo B, Shi PY, Verma S. Combined treatment of adenosine nucleoside inhibitor NITD008 and histone deacetylase inhibitor vorinostat represents an immunotherapy strategy to ameliorate West Nile virus infection. Antiviral Res. 2015;122:39–45.

70. Coussens AK, Wilkinson RJ, Martineau AR. Phenylbutyrate Is Bacteriostatic against Mycobacterium tuberculosis and Regulates the Macrophage Response to Infection, Synergistically with 25-Hydroxy-Vitamin D(3). PLoS Pathog. 2015;11(7):e1005007.

71. Mily A, Rekha RS, Kamal SM, Arifuzzaman AS, Rahim Z, Khan L, Haq MA, Zaman K, Bergman P, Brighenti S, et al. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. PLoS One. 2015;10(9):e0138340.

72. Wallis RS, van Vuuren C, Potgieter S. Adalimumab treatment of lifethreatening tuberculosis. Clin Infect Dis. 2009;48(10):1429–32.

73. Casarini M, Ameglio F, Alemanno L, Zangrilli P, Mattia P, Paone G, Bisetti A, Giosue S. Cytokine levels correlate with a radiologic score in active pulmonary tuberculosis. Am J Respir Crit Care Med. 1999;159(1):143–8.

74. Chowdhury IH, Ahmed AM, Choudhuri S, Sen A, Hazra A, Pal NK, Bhattacharya B, Bahar B. Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy. Mol Immunol. 2014;62(1):159–68.

75. Okada M, Kita Y, Kanamaru N, Hashimoto S, Uchiyama Y, Mihara M, Inoue Y, Ohsugi Y, Kishimoto T, Sakatani M. Anti-IL-6 receptor antibody causes less promotion of tuberculosis infection than anti-TNF-alpha antibody in mice. Clin Dev Immunol. 2011;2011:404929.

76. Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, Nakano N, Ikeda Y, Sasaki T, Nishioka K, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood. 2005;106(8):2627–32.

77. van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fossa A, Simpson D, Capra M, Liu T, Hsieh RK, et al. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966–74.

78. Guo Y, Xu F, Lu T, Duan Z, Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev. 2012;38(7):904–10.

79. Datta M, Via LE, Kamoun WS, Liu C, Chen W, Seano G, Weiner DM, Schimel D, England K, Martin JD, et al. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. Proc Natl Acad Sci U S A. 2015;112(6):1827–32.

80. Oehlers SH, Cronan MR, Scott NR, Thomas MI, Okuda KS, Walton EM, Beerman RW, Crosier PS, Tobin DM. Interception of host angiogenic signalling limits mycobacterial growth. Nature. 2015;517(7536):612–5.

81. Veenstra H, Baumann R, Lukey PT, Beyers N, van Helden PD, Walzl G. High levels of intracellular IL-4 are expressed in circulating apoptotic T cells in patients with tuberculosis and in community controls. Tuberculosis. 2008;88(1):21–30.

82. Roberts T, Beyers N, Aguirre A, Walzl G. Immunosuppression during active tuberculosis is characterized by decreased interferon- gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor- beta, and interleukin-4 mRNA levels. J Infect Dis. 2007;195(6):870–8.

83. Heitmann L, Abad Dar M, Schreiber T, Erdmann H, Behrends J, McKenzie AN, Brombacher F, Ehlers S, Holscher C. The IL-13/IL-4Ralpha axis is involved in tuberculosis-associated pathology. J Pathol. 2014;234(3):338–50.

84. Chen H, Cheng C, Li M, Gao S, Li S, Sun H. Expression of TNF-alpha, IFN-gamma, TGF-beta, and IL-4 in the spinal tuberculous focus and its impact on the disease. Cell Biochem Biophys. 2014;70(3):1759–64.

85. Rahman S, Rehn A, Rahman J, Andersson J, Svensson M, Brighenti S. Pulmonary tuberculosis patients with a vitamin D deficiency demonstrate low local expression of the antimicrobial peptide LL-37 but enhanced FoxP3 regulatory T cells and IgG-secreting cells. Clin Immunol. 2014;156(2):85–97.

86. Montoya D, Inkeles MS, Liu PT, Realegeno S, Teles RM, Vaidya P, Munoz MA, Schenk M, Swindell WR, Chun R, et al. IL-32 is a molecular marker of a host defense network in human tuberculosis. Sci Transl Med. 2014;6(250):250ra114.

87. Klug-Micu GM, Stenger S, Sommer A, Liu PT, Krutzik SR, Modlin RL, Fabri M. CD40 ligand and interferon-gamma induce an antimicrobial response against Mycobacterium tuberculosis in human monocytes. Immunology. 2013;139(1):121–8.

88. Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, Suzana S, Jeyaseelan L, Christopher DJ, Smieja M, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2015;15(5):528–34.

89. Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Easley KA, Shenvi N, Kempker RR, Frediani JK, Mirtskhulava V, Alvarez JA, et al. High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. Am J Clin Nutr. 2015;102(5):1059–69.

90. Azoury SC, Straughan DM, Shukla V. Immune Checkpoint Inhibitors for Cancer Therapy: Clinical Efficacy and Safety. Curr Cancer Drug Targets. 2015;15(6):452–62.

91. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.

92. Leung J, Suh WK. The CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy. Immune Netw. 2014;14(6):265–76.

93. Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219–42.

94. Srahna M, Van Grunsven LA, Remacle JE, Vandenberghe P. CTLA-4 interacts with STAT5 and inhibits STAT5-mediated transcription. Immunology. 2006;117(3):396–401.

95. Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3 - potential mechanisms of action. Nat Rev Immunol. 2014;15(1):45–56.

96. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56–61.

97. Gardiner D, Lalezari J, Lawitz E, DiMicco M, Ghalib R, Reddy KR, Chang KM, Sulkowski M, Marro SO, Anderson J, et al. A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection. PLoS One. 2013;8(5):e63818.

98. Jurado JO, Alvarez IB, Pasquinelli V, Martinez GJ, Quiroga MF, Abbate E, Musella RM, Chuluyan HE, Garcia VE. Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis. J Immunol. 2008;181(1):116–25.

99. Singh A, Mohan A, Dey AB, Mitra DK. Inhibiting the programmed death 1 pathway rescues Mycobacterium tuberculosis-specific interferon gammaproducing T cells from apoptosis in patients with pulmonary tuberculosis. J Infect Dis. 2013;208(4):603–15.

100. Hassan SS, Akram M, King EC, Dockrell HM, Cliff JM. PD-1, PD-L1 and PD-L2 Gene Expression on T-Cells and Natural Killer Cells Declines in Conjunction with a Reduction in PD-1 Protein during the Intensive Phase of Tuberculosis Treatment. PLoS One. 2015;10(9):e0137646.

101. McNab FW, Berry MP, Graham CM, Bloch SA, Oni T, Wilkinson KA, Wilkinson RJ, Kon OM, Banchereau J, Chaussabel D, et al. Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis. Eur J Immunol. 2011;41(7):1941–7.

102. Singh A, Dey AB, Mohan A, Mitra DK. Programmed death-1 receptor suppresses gamma-IFN producing NKT cells in human tuberculosis. Tuberculosis. 2014;94(3):197–206.

103. Garcia Jacobo RE, Serrano CJ, Enciso Moreno JA, Gaspar Ramirez O, Trujillo Ochoa JL, Uresti Rivera EE, Portales Perez DP, Gonzalez-Amaro R, Garcia Hernandez MH. Analysis of Th1, Th17 and regulatory T cells in tuberculosis case contacts. Cell Immunol. 2014;289(1-2):167–73.

104. Merlo A, Saverino D, Tenca C, Grossi CE, Bruno S, Ciccone E. CD85/LIR-1/ILT2 and CD152 (cytotoxic T lymphocyte antigen 4) inhibitory molecules downregulate the cytolytic activity of human CD4+ T-cell clones specific for Mycobacterium tuberculosis. Infect Immun. 2001;69(10):6022–9.

105. Sierro S, Romero P, Speiser DE. The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin Ther Targets. 2011;15(1):91–101.

106. Phillips BL, Mehra S, Ahsan MH, Selman M, Khader SA, Kaushal D. LAG3 Expression in Active Mycobacterium tuberculosis Infections. Am J Pathol. 2014. doi:10.1016/j.ajpath.2014.11.003.

107. Butler NS, Moebius J, Pewe LL, Traore B, Doumbo OK, Tygrett LT, Waldschmidt TJ, Crompton PD, Harty JT. Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. Nat Immunol. 2012;13(2):188–95.

108. Ngiow SF, Teng MW, Smyth MJ. Prospects for TIM3-Targeted Antitumor Immunotherapy. Cancer Res. 2011;71(21):6567–71.

109. Sada-Ovalle I, Chavez-Galan L, Torre-Bouscoulet L, Nava-Gamino L, Barrera L, Jayaraman P, Torres-Rojas M, Salazar-Lezama MA, Behar SM. The Tim3-galectin 9 pathway induces antibacterial activity in human macrophages infected with Mycobacterium tuberculosis. J Immunol. 2012;189(12):5896–902.

110. Sada-Ovalle I, Ocana-Guzman R, Perez-Patrigeon S, Chavez-Galan L, Sierra-Madero J, Torre-Bouscoulet L, Addo MM. Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients. J Int AIDS Soc. 2015;18(1):20078.

111. Parida SK, Poiret T, Zhenjiang L, Meng Q, Heyckendorf J, Lange C, Ambati AS, Rao MV, Valentini D, Ferrara G, et al. T-Cell Therapy: Options for Infectious Diseases. Clin Infect Dis. 2015;61 suppl 3:S217–24.

112. Parida SK, Madansein R, Singh N, Padayatchi N, Master I, Naidu K, Zumla A, Maeurer M. Cellular therapy in tuberculosis. Int J Infect Dis. 2015;32:32–8.

113. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348(6230):62–8.

114. Skrahin A, Ahmed RK, Ferrara G, Rane L, Poiret T, Isaikina Y, Skrahina A, Zumla A, Maeurer MJ. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir Med. 2014;2(2):108–22.

115. Cho S, Mehra V, Thoma-Uszynski S, Stenger S, Serbina N, Mazzaccaro RJ, Flynn JL, Barnes PF, Southwood S, Celis E, et al. Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis. Proc Natl Acad Sci U S A. 2000;97(22):12210–5.

116. Mustafa AS, Oftung F, Amoudy HA, Madi NM, Abal AT, Shaban F, Rosen Krands I, Andersen P. Multiple epitopes from the Mycobacterium tuberculosis ESAT-6 antigen are recognized by antigen-specific human T cell lines. Clin Infect Dis. 2000;30 Suppl 3:S201–205.

117. Kasmar AG, Van Rhijn I, Magalhaes KG, Young DC, Cheng TY, Turner MT, Schiefner A, Kalathur RC, Wilson IA, Bhati M, et al. Cutting Edge: CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo. J Immunol. 2013;191(9):4499–503.

118. Axelsson-Robertson R, Rao M, Loxton AG, Walzl G, Bates M, Zumla A, Maeurer M. Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment. Int J Infect Dis. 2015;32:23–9.

119. El Daker S, Sacchi A, Montesano C, Altieri AM, Galluccio G, Colizzi V, Martini F, Martino A. An abnormal phenotype of lung Vgamma9Vdelta2 T cells impairs their responsiveness in tuberculosis patients. Cell Immunol. 2013;282(2):106–12.

120. Beeson CC, Beeson GC, Schnellmann RG. A high-throughput respirometric assay for mitochondrial biogenesis and toxicity. Anal Biochem. 2010;404(1):75–81.

121. Roca FJ, Ramakrishnan L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell. 2013;153(3):521–34.

122. Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005;366(9485):549–55.

123. Tung EW, Winn LM. Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: a role for oxidative stress in valproic acid-induced neural tube defects. Mol Pharmacol. 2011;80(6):979–87.

124. Schiebler M, Brown K, Hegyi K, Newton SM, Renna M, Hepburn L, Klapholz C, Coulter S, Obregon-Henao A, Henao Tamayo M, et al. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion. EMBO Mol Med. 2015;7(2):127–39.

125. Sung JA, Lam S, Garrido C, Archin N, Rooney CM, Bollard CM, Margolis DM. Expanded Cytotoxic T-cell Lymphocytes Target the Latent HIV Reservoir. J Infect Dis. 2015. doi:10.1093/infdis/jiv022.

126. Petruccelli LA, Dupere-Richer D, Pettersson F, Retrouvey H, Skoulikas S, Miller Jr WH. Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells. PLoS One. 2011;6(6):e20987.

127. Marks PA, Richon VM, Kelly WK, Chiao JH, Miller T. Histone deacetylase inhibitors: development as cancer therapy. Novartis Found Symp. 2004;259: 269–81. discussion 281-268.

128. Kulkarni NN, Yi Z, Huehnken C, Agerberth B, Gudmundsson GH. Phenylbutyrate induces cathelicidin expression via the vitamin D receptor: Linkage to inflammatory and growth factor cytokines pathways. Mol Immunol. 2015;63(2):530–9.

129. Zhao J, Cao Y, Lei Z, Yang Z, Zhang B, Huang B. Selective depletion of CD4 + CD25 + Foxp3+ regulatory T cells by low-dose cyclophosphamide is explained by reduced intracellular ATP levels. Cancer Res. 2010;70(12):4850–8.

130. Henter JI, Palmkvist-Kaijser K, Holzgraefe B, Bryceson YT, Palmer K. Cytotoxic therapy for severe swine flu A/H1N1. Lancet. 2010;376(9758):2116.

131. Pirinen E, Canto C, Jo YS, Morato L, Zhang H, Menzies KJ, Williams EG, Mouchiroud L, Moullan N, Hagberg C, et al. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab. 2014;19(6):1034–41.

132. Zumla A, Bates M, Maeurer M. Corticosteroid therapy for pneumonia. Lancet. 2015;386(9997):955.

133. Singh NP, Hegde VL, Hofseth LJ, Nagarkatti M, Nagarkatti P. Resveratrol (trans-3,5,4′-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. Mol Pharmacol. 2007;72(6):1508–21.

134. Estrella JL, Kan-Sutton C, Gong X, Rajagopalan M, Lewis DE, Hunter RL, Eissa NT, Jagannath C. A Novel in vitro Human Macrophage Model to Study the Persistence of Mycobacterium tuberculosis Using Vitamin D(3) and Retinoic Acid Activated THP-1 Macrophages. Front Microbiol. 2011;2:67.

135. van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ, Pearce EL. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2012;36(1):68–78.

136. Oh S, Perera LP, Terabe M, Ni L, Waldmann TA, Berzofsky JA. IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAILmediated apoptosis. Proc Natl Acad Sci U S A. 2008;105(13):5201–6.

137. Borch TH, Donia M, Andersen MH, Svane IM. Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies. Drug Discov Today. 2015. doi:10.1016/j.drudis.2015.07.003.

138. Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, et al. Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2015;33(18):2004–12.

139. Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, et al. PD-1 identifies the patient-specific CD8(+) tumorreactive repertoire infiltrating human tumors. J Clin Invest. 2014;124(5):2246–59.

140. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.

141. Niezgoda A, Niezgoda P, Czajkowski R. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy. BioMed Res Int. 2015;2015:851387.

142. Goovaerts O, Jennes W, Massinga-Loembe M, Ceulemans A, Worodria W, Mayanja-Kizza H, Colebunders R, Kestens L, Group T-IS. LPS-binding protein and IL-6 mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients. PLoS One. 2013;8(11):e81856.

143. Rossi JF, Lu ZY, Jourdan M, Klein B. Interleukin-6 as a therapeutic target. Clin Cancer Res. 2015;21(6):1248–57.

144. Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol. 2013;31(9):1219–30.

145. Joshi L, Chelluri LK, Gaddam S. Mesenchymal Stromal Cell Therapy in MDR/XDR Tuberculosis: A Concise Review. Arch Immunol Ther Exp (Warsz). 2015. doi:10.1007/s00005-015-0347-9.

146. Axelsson-Robertson R, Loxton AG, Walzl G, Ehlers MM, Kock MM, Zumla A, Maeurer M. A Broad Profile of Co-Dominant Epitopes Shapes the Peripheral Mycobacterium tuberculosis Specific CD8+ T-Cell Immune Response in South African Patients with Active Tuberculosis. PLoS One. 2013;8(3):e58309.

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