Abstract
For centuries the treatment of TB has presented an enormous challenge to global health. In the 20th century, the treatment of TB patients with long-term multidrug therapy gave hope that TB could be controlled and cured; however, contrary to these expectations and coinciding with the emergence of AIDS, the world has witnessed a rampant increase in hard-to-treat cases of TB, along with the emergence of highly virulent and multidrug-resistant Mycobacterium tuberculosis strains. Unfortunately, these bacteria are now circulating around the world, and there are few effective drugs to treat them. As a result, the prospects for improved treatment and control of TB in the 21st century have worsened and we urgently need to identify new therapies that deal with this problem. The potential use of immunotherapy for TB is now of greater consideration than ever before, as immunotherapy could potentially overcome the problem of drug resistance. TB immunotherapy targets the already existing host anti-TB immune response and aims to enhance killing of the bacilli. For this purpose, several approaches have been used: the use of anti-Mycobacteria antibodies; enhancing the Th1 protective responses by using mycobacterial antigens or increasing Th1 cytokines; interfering with the inflammatory process and targeting of immunosuppressive pathways and targeting the cell activation/proliferation pathways. This article reviews our current understanding of TB immunity and targets for immunotherapy that could be used in combination with current TB chemotherapy.
Papers of special note have been highlighted as: ▪ of interest
References
- 1 Palanisamy GS, Smith EE, Shanley CA, Ordway DJ, Orme IM, Basaraba RJ. Disseminated disease severity as a measure of virulence of Mycobacterium tuberculosis in the guinea pig model. Tuberculosis (Edinb.)88(4),295–306 (2008).Crossref, Medline, Google Scholar
- 2 Gupta KB, Gupta R, Atreja A, Verma M, Vishvkarma S. Tuberculosis and nutrition. Lung India26(1),9–16 (2009).Crossref, Medline, Google Scholar
- 3 Madebo T, Lindtjorn B, Aukrust P, Berge RK. Circulating antioxidants and lipid peroxidation products in untreated tuberculosis patients in Ethiopia. Am. J. Clin. Nutr.78(1),117–122 (2003).Crossref, Medline, CAS, Google Scholar
- 4 Chandra RK. Nutrient supplementation as adjunct therapy in pulmonary tuberculosis. Int. J. Vitam. Nutr. Res.74(2),144–146 (2004).Crossref, Medline, CAS, Google Scholar
- 5 Armijos RX, Weigel MM, Chacon R, Flores L, Campos A. Adjunctive micronutrient supplementation for pulmonary tuberculosis. Salud Publica. Mex.52(3),185–189 (2010).Crossref, Medline, Google Scholar
- 6 Martineau AR, Wilkinson RJ, Wilkinson KA et al. A single dose of vitamin D enhances immunity to mycobacteria. Am. J. Respir. Crit. Care Med.176(2),208–213 (2007).Crossref, Medline, CAS, Google Scholar
- 7 Schon T, Idh J, Westman A et al. Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis – a randomised trial. Tuberculosis (Edinb.)91(5),370–377 (2011).Crossref, Medline, CAS, Google Scholar
- 8 Schon T, Elias D, Moges F et al. Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis. Eur. Respir. J.21(3),483–488 (2003).Crossref, Medline, CAS, Google Scholar
- 9 Arjanova OV, Prihoda ND, Yurchenko LV et al. Enhancement of efficacy of tuberculosis drugs with immunoxel (Dzherelo) in HIV-infected patients with active pulmonary tuberculosis. Immunotherapy1(4),549–556 (2009).Link, CAS, Google Scholar
- 10 Bodnar PM, Mykhal’chyshyn HP, Reznichenko VM, Moshchych OP, Pylypchuk VS. Phytoconcentrates “dzherelo” and “lizorm” in therapy of autoimmune thyroiditis. Lik. Sprava. (8), 127–129 (2002).Medline, Google Scholar
- 11 Nikolaeva LG, Maystat TV, Masyuk LA, Pylypchuk VS, Volyanskii YL, Kutsyna GA. Changes in CD4+ T-cells and HIV RNA resulting from combination of anti-TB therapy with Dzherelo in TB/HIV dually infected patients. Drug Des. Dev. Ther.2,87–93 (2009).Medline, Google Scholar
- 12 Nikolaeva LG, Maystat TV, Pylypchuk VS, Volyanskii YL, Frolov VM, Kutsyna GA. Cytokine profiles of HIV patients with pulmonary tuberculosis resulting from adjunct immunotherapy with herbal phytoconcentrates Dzherelo and Anemin. Cytokine44(3),392–396 (2008).Crossref, Medline, CAS, Google Scholar
- 13 Abba K, Sudarsanam TD, Grobler L, Volmink J. Nutritional supplements for people being treated for active tuberculosis. Cochrane Database Syst. Rev.4,CD006086 (2008).Medline, Google Scholar
- 14 Kennedy N, Ramsay A, Uiso L, Gutmann J, Ngowi FI, Gillespie SH. Nutritional status and weight gain in patients with pulmonary tuberculosis in Tanzania. Trans. R. Soc. Trop. Med. Hyg.90(2),162–166 (1996).Crossref, Medline, CAS, Google Scholar
- 15 Sturgill-Koszycki S, Schlesinger PH, Chakraborty P et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science263(5147),678–681 (1994).Crossref, Medline, CAS, Google Scholar
- 16 Orme IM, Cooper AM. Cytokine/chemokine cascades in immunity to tuberculosis. Immunol. Today20(7),307–312 (1999).Crossref, Medline, CAS, Google Scholar
- 17 Voskuil MI, Schnappinger D, Visconti KC et al. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med.198(5),705–713 (2003).Crossref, Medline, CAS, Google Scholar
- 18 Voskuil MI, Visconti KC, Schoolnik GK. Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy. Tuberculosis (Edinb.)84(3–4),218–227 (2004).Crossref, Medline, CAS, Google Scholar
- 19 Gonzalez-Juarrero M, Turner OC, Turner J, Marietta P, Brooks JV, Orme IM. Temporal and spatial arrangement of lymphocytes within lung granulomas induced by aerosol infection with Mycobacterium tuberculosis. Infect. Immun.69(3),1722–1728 (2001).Crossref, Medline, CAS, Google Scholar
- 20 Ulrichs T, Kosmiadi GA, Trusov V et al. Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung. J. Pathol.204(2),217–228 (2004).Crossref, Medline, Google Scholar
- 21 Ordway D, Henao-Tamayo M, Orme IM, Gonzalez-Juarrero M. Foamy macrophages within lung granulomas of mice infected with Mycobacterium tuberculosis express molecules characteristic of dendritic cells and antiapoptotic markers of the TNF receptor-associated factor family. J. Immunol.175(6),3873–3881 (2005).Crossref, Medline, CAS, Google Scholar
- 22 Glatman-Freedman A. Advances in antibody-mediated immunity against Mycobacterium tuberculosis: implications for a novel vaccine strategy. FEMS Immunol. Med. Microbiol.39(1),9–16 (2003).Crossref, Medline, CAS, Google Scholar
- 23 Peresi E, Silva SM, Calvi SA, Marcondes-Machado J. Cytokines and acute phase serum proteins as markers of inflammatory regression during the treatment of pulmonary tuberculosis. J. Bras. Pneumol.34(11),942–949 (2008).Crossref, Medline, Google Scholar
- 24 Eum SY, Lee YJ, Min JH et al. Association of antigen-stimulated release of tumor necrosis factor-α in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis. Respiration80(4),275–284 (2010).Crossref, Medline, CAS, Google Scholar
- 25 Ameglio F, Casarini M, Capoluongo E, Mattia P, Puglisi G, Giosue S. Post-treatment changes of six cytokines in active pulmonary tuberculosis: differences between patients with stable or increased fibrosis. Int. J. Tuberc. Lung Dis.9(1),98–104 (2005).Medline, CAS, Google Scholar
- 26 Ordway DJ, Shang S, Henao-Tamayo M et al. BCG mediated protection against W-Beijing strains of Mycobacterium tuberculosis is diminished concomitant with the emergence of regulatory T cells. Clin. Vacc. Immunol.18(9),1527–1535 (2011).Crossref, Medline, CAS, Google Scholar
- 27 Shang S, Harton M, Tamayo MH et al. Increased FoxP3 expression in guinea pigs infected with W-Beijing strains of M. Tuberculosis. Tuberculosis (Edinb.)91(5),378–385 (2011).Crossref, Medline, CAS, Google Scholar
- 28 Keane J. TNF-blocking agents and tuberculosis: new drugs illuminate an old topic. Rheumatology (Oxf.)44(6),714–720 (2005).Crossref, Medline, CAS, Google Scholar
- 29 Ordway D, Higgins DM, Sanchez-Campillo J et al. XCL1 (lymphotactin) chemokine produced by activated CD8 T cells during the chronic stage of infection with Mycobacterium tuberculosis negatively affects production of IFN-γ by CD4 T cells and participates in granuloma stability. J. Leukoc. Biol.82(5),1221–1229 (2007).Crossref, Medline, CAS, Google Scholar
- 30 Prideaux B, Dartois VR, Staab D et al. High-sensitivity MALDI-MRM-MS imaging of moxifloxacin distribution in tuberculosis-infected rabbit lungs and granulomatous lesions. Analyt. Chem.83(6),2112–2118 (2011).Crossref, Medline, CAS, Google Scholar
- 31 Wallis RS, Kyambadde P, Johnson JL et al. A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS18(2),257–264 (2004).▪ TNF blockade and association with the reactivation of latent Mycobacterium tuberculosis infection by the impairment of mycobacterial immunity.Crossref, Medline, CAS, Google Scholar
- 32 Brock DT. Robert Koch: a Life in Medicine and Bacteriology. American Society for Microbiology Press, Washington, DC, USA, 20005–24171 (1999).Google Scholar
- 33 Cardona PJ. RUTI: a new chance to shorten the treatment of latent tuberculosis infection. Tuberculosis (Edinb.)86(3–4),273–289 (2006).▪ Rationale for combining immunotherapy with chemotherapy. The use of mycobacteria antigens to enhance immune killing of the bacteria.Crossref, Medline, Google Scholar
- 34 Vilaplana C, Montane E, Pinto S et al. Double-blind, randomized, placebo-controlled Phase 1 clinical trial of the therapeutical antituberculous vaccine RUTI. Vaccine28(4),1106–1116 (2010).Crossref, Medline, CAS, Google Scholar
- 35 Vilaplana C, Gil O, Caceres N, Pinto S, Diaz J, Cardona PJ. Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis. PLoS ONE6(5),E20404 (2011).Crossref, Medline, CAS, Google Scholar
- 36 Corlan E, Marica C, Macavei C, Stanford JL, Stanford CA. Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 2. Chronic or relapsed disease. Respir. Med.91(1),21–29 (1997).Crossref, Medline, CAS, Google Scholar
- 37 Dlugovitzky D, Bottasso O, Dominino JC et al. Clinical and serological studies of tuberculosis patients in Argentina receiving immunotherapy with Mycobacterium vaccae (SRL 172). Respir. Med.93(8),557–562 (1999).Crossref, Medline, CAS, Google Scholar
- 38 Dlugovitzky D, Stanford C, Stanford J. Immunological basis for the introduction of immunotherapy with Mycobacterium vaccae into the routine treatment of TB. Immunotherapy3(4),557–568 (2011).Link, CAS, Google Scholar
- 39 Johnson JL, Kamya RM, Okwera A et al. Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected Ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration. J. Infect. Dis.181(4),1304–1312 (2000).▪ Adjunctive immunotherapy with heat-killed Mycobacterium vaccae in a randomized, placebo-controlled trial of nonhuman immunodeficiency virus-infected adults with newly diagnosed pulmonary TB.Crossref, Medline, CAS, Google Scholar
- 40 Johnson JL, Nunn AJ, Fourie PB et al. Effect of Mycobacterium vaccae (SRL172) immunotherapy on radiographic healing in tuberculosis. Int. J. Tuberc. Lung Dis.8(11),1348–1354 (2004).Medline, CAS, Google Scholar
- 41 Lahey T, Arbeit RD, Bakari M et al. Immunogenicity of a protective whole cell mycobacterial vaccine in HIV-infected adults: a Phase 3 study in Tanzania. Vaccine28(48),7652–7658 (2010).Crossref, Medline, Google Scholar
- 42 Onyebujoh PC, Abdulmumini T, Robinson S, Rook GA, Stanford JL. Immunotherapy with Mycobacterium vaccae as an addition to chemotherapy for the treatment of pulmonary tuberculosis under difficult conditions in Africa. Respir. Med.89(3),199–207 (1995).Crossref, Medline, CAS, Google Scholar
- 43 Stanford J, Stanford C, Grange J. Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis. Front. Biosci.9,1701–1719 (2004).Crossref, Medline, CAS, Google Scholar
- 44 Vuola JM, Ristola MA, Cole B et al. Immunogenicity of an inactivated mycobacterial vaccine for the prevention of HIV-associated tuberculosis: a randomized, controlled trial. AIDS17(16),2351–2355 (2003).Crossref, Medline, CAS, Google Scholar
- 45 Wang W, Jin G, Ye Y et al. A clinical study on vaccine of Mycobacterium vaccae in treating pulmonary tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi22(2),108–110 (1999).Medline, CAS, Google Scholar
- 46 Waddell RD, Chintu C, Lein AD et al. Safety and immunogenicity of a five-dose series of inactivated Mycobacterium vaccae vaccination for the prevention of HIV-associated tuberculosis. Clin. Infect. Dis.30(Suppl. 3),S309–S315 (2000).Crossref, Medline, Google Scholar
- 47 Von Reyn CF, Mtei L, Arbeit RD et al. Prevention of tuberculosis in bacille calmette-guerin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS24(5),675–685 (2010).Crossref, Medline, Google Scholar
- 48 Baroux N, D’Ortenzio E. Tuberculosis in reunion island: epidemiological characteristics of notified cases, 2000–2007. Med. Mal. Infect.40(1),12–17 (2010).Crossref, Medline, CAS, Google Scholar
- 49 Mwinga A, Nunn A, Ngwira B et al.Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial. Lancet360(9339),1050–1055 (2002).Crossref, Medline, Google Scholar
- 50 Orme IM. Development of new vaccines and drugs for TB: limitations and potential strategic errors. Future Microbiol.6(2),161–177 (2011).Link, CAS, Google Scholar
- 51 Rook GAW, Lowrie DB, Hernndez-Pando R. Immunotherapeutics for tuberculosis in experimental animals: is there a common pathway activated by effective protocols? J. Infect. Dis.196(2),191–198 (2007).Crossref, Medline, CAS, Google Scholar
- 52 Holland SM. Cytokine therapy of mycobacterial infections. Adv. Intern. Med.45,431–452 (2000).Medline, CAS, Google Scholar
- 53 Tomioka H. Adjunctive immunotherapy of mycobacterial infections. Curr. Pharm. Des.10(26),3297–3312 (2004).Crossref, Medline, CAS, Google Scholar
- 54 Toossi Z. Adjunctive immunotherapy of tuberculosis. Cytokines Cell Mol. Ther.4(2),105–112 (1998).▪ Early report on the use of cytokines as adjunctive immunotherapy in the management of difficult-to-treat TB or TB in the immunodeficient host.Medline, CAS, Google Scholar
- 55 Tsuyuguchi I. Immunotherapy for MDR-TB (multi-drug resistant tuberculosis) – its feasibility. Kekkaku74(6),479–491 (1999).Medline, CAS, Google Scholar
- 56 Churchyard GJ, Kaplan G, Fallows D, Wallis RS, Onyebujoh P, Rook GA. Advances in immunotherapy for tuberculosis treatment. Clin. Chest Med.30(4),769–782, ix (2009).Crossref, Medline, Google Scholar
- 57 Ribeiro-Rodrigues R, Resende CoT, Johnson JL et al. Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance. Clin. Diagn. Lab. Immunol.9(4),818–823 (2002).Medline, CAS, Google Scholar
- 58 Djoba Siawaya JF, Beyers N, Van Helden P, Walzl G. Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis. Clin. Exp. Immunol.156(1),69–77 (2009).Crossref, Medline, CAS, Google Scholar
- 59 Berktas M, Guducuoglu H, Bozkurt H, Onbasi KT, Kurtoglu MG, Andic S. Change in serum concentrations of interleukin-2 and interferon-γ during treatment of tuberculosis. J. Int. Med. Res.32(3),324–330 (2004).Crossref, Medline, CAS, Google Scholar
- 60 Johnson B, Bekker LG, Ress S, Kaplan G. Recombinant interleukin 2 adjunctive therapy in multidrug-resistant tuberculosis. Novartis Found. Symp.217,99–106 (1998).Crossref, Medline, CAS, Google Scholar
- 61 Johnson BJ, Estrada I, Shen Z et al. Differential gene expression in response to adjunctive recombinant human interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients. Infect. Immun.66(6),2426–2433 (1998).Crossref, Medline, CAS, Google Scholar
- 62 Johnson BJ, Ress SR, Willcox P et al. Clinical and immune responses of tuberculosis patients treated with low-dose IL-2 and multidrug therapy. Cytokines Mol. Ther.1(3),185–196 (1995).Medline, CAS, Google Scholar
- 63 Johnson JL, Ssekasanvu E, Okwera A et al. Randomized trial of adjunctive interleukin-2 in adults with pulmonary tuberculosis. Am. J. Respir. Crit. Care Med.168(2),185–191 (2003).Crossref, Medline, Google Scholar
- 64 Gao XF, Yang ZW, Li J. Adjunctive therapy with interferon-γ for the treatment of pulmonary tuberculosis: a systematic review. Int. J. Infect. Dis.15(9),E594–E600 (2011).Crossref, Medline, CAS, Google Scholar
- 65 Giosue S, Casarini M, Alemanno L et al. Effects of aerosolized interferon-α in patients with pulmonary tuberculosis. Am. J. Respir. Crit. Care Med.158(4),1156–1162 (1998).Crossref, Medline, CAS, Google Scholar
- 66 Hirsch CS, Toossi Z, Othieno C et al. Depressed T-cell interferon-γ responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J. Infect. Dis.180(6),2069–2073 (1999).Crossref, Medline, CAS, Google Scholar
- 67 Murray HW. Interferon-γ and host antimicrobial defense: current and future clinical applications. Am. J. Med.97(5),459–467 (1994).Crossref, Medline, CAS, Google Scholar
- 68 Reljic R. IFN-γ therapy of tuberculosis and related infections. J. Interferon Cytokine Res.27(5),353–364 (2007).Crossref, Medline, CAS, Google Scholar
- 69 Schluger NW, Perez D, Liu YM. Reconstitution of immune responses to tuberculosis in patients with HIV infection who receive antiretroviral therapy. Chest122(2),597–602 (2002).Crossref, Medline, Google Scholar
- 70 Suarez-Mendez R, Garcia-Garcia I, Fernandez-Olivera N et al. Adjuvant interferon γ in patients with drug-resistant pulmonary tuberculosis: a pilot study. BMC Infect. Dis.4,44 (2004).Crossref, Medline, Google Scholar
- 71 Greinert U, Ernst M, Schlaak M, Entzian P. Interleukin-12 as successful adjuvant in tuberculosis treatment. Eur. Respir. J.17(5),1049–1051 (2001).Crossref, Medline, CAS, Google Scholar
- 72 Nolt D, Flynn JL. Interleukin-12 therapy reduces the number of immune cells and pathology in lungs of mice infected with Mycobacterium tuberculosis. Infect. Immun.72(5),2976–2988 (2004).Crossref, Medline, CAS, Google Scholar
- 73 Olmos S, Stukes S, Ernst JD. Ectopic activation of Mycobacterium tuberculosis-specific CD4+ T cells in lungs of CCR7-/- mice. J. Immunol.184(2),895–901 (2010).Crossref, Medline, CAS, Google Scholar
- 74 Gonzalez-Juarrero M, Turner J, Basaraba RJ, Belisle JT, Orme IM. Florid pulmonary inflammatory responses in mice vaccinated with antigen-85 pulsed dendritic cells and challenged by aerosol with Mycobacterium tuberculosis. Cell. Immunol.220(1),13–19 (2002).Crossref, Medline, CAS, Google Scholar
- 75 Kaplan G, Post FA, Moreira AL et al.Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity. Infect. Immun.71(12),7099–7108 (2003).Crossref, Medline, CAS, Google Scholar
- 76 Gonzalez-Juarrero M, Kingry LC, Ordway DJ et al. Immune response to Mycobacterium tuberculosis and identification of molecular markers of disease. Am. J. Respir. Cell Mol. Biol.40(4),398–409 (2009).Crossref, Medline, CAS, Google Scholar
- 77 Taylor JL, Ordway DJ, Troudt J, Gonzalez-Juarrero M, Basaraba RJ, Orme IM. Factors associated with severe granulomatous pneumonia in Mycobacterium tuberculosis-infected mice vaccinated therapeutically with hsp65 DNA. Infect. Immun.73(8),5189–5193 (2005).Crossref, Medline, CAS, Google Scholar
- 78 Kaplan G. Cytokine regulation of disease progression in leprosy and tuberculosis. Immunobiology191(4–5),564–568 (1994).Crossref, Medline, CAS, Google Scholar
- 79 Gutierrez-Rodriguez O. Thalidomide. A promising new treatment for rheumatoid arthritis. Arthrit. Rheum.27(10),1118–1121 (1984).Crossref, Medline, CAS, Google Scholar
- 80 Tramontana JM, Utaipat U, Molloy A et al. Thalidomide treatment reduces tumor necrosis factor α production and enhances weight gain in patients with pulmonary tuberculosis. Mol. Med.1(4),384–397 (1995).▪ Use of thalidomide as a TNF-α blocker in the treatment of TB.Crossref, Medline, CAS, Google Scholar
- 81 Tsenova L, Sokol K, Freedman VH, Kaplan G. A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death. J. Infect. Dis.177(6),1563–1572 (1998).Crossref, Medline, CAS, Google Scholar
- 82 Corral LG, Muller GW, Moreira AL et al. Selection of novel analogs of thalidomide with enhanced tumor necrosis factor α inhibitory activity. Mol. Med.2(4),506–515 (1996).Crossref, Medline, CAS, Google Scholar
- 83 Koo MS, Manca C, Yang G et al. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice. PLoS ONE6(2),E17091 (2011).Crossref, Medline, CAS, Google Scholar
- 84 Tsenova L, Mangaliso B, Muller G et al. Use of IMiD3, a thalidomide analog, as an adjunct to therapy for experimental tuberculous meningitis. Antimicrob. Agents Chemother.46(6),1887–1895 (2002).Crossref, Medline, CAS, Google Scholar
- 85 Wallis RS. Reactivation of latent tuberculosis by TNF blockade: the role of interferon γ. J. Investig. Dermatol. Symp. Proc.12(1),16–21 (2007).Crossref, Medline, CAS, Google Scholar
- 86 Wyser C, Walzl G, Smedema JP, Swart F, van Schalkwyk EM, van De Wal BW. Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study. Chest110(2),333–338 (1996).Crossref, Medline, CAS, Google Scholar
- 87 Mayanja-Kizza H, Jones-Lopez E, Okwera A et al. Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a Phase 2 clinical trial in Uganda. J. Infect. Dis.191(6),856–865 (2005).Crossref, Medline, CAS, Google Scholar
- 88 Wallis RS. Reconsidering adjuvant immunotherapy for tuberculosis. Clin. Infect. Dis.41(2),201–208 (2005).Crossref, Medline, CAS, Google Scholar
- 89 Byrne ST, Denkin SM, Zhang Y. Aspirin and ibuprofen enhance pyrazinamide treatment of murine tuberculosis. J. Antimicrob. Chemother.59(2),313–316 (2007).Crossref, Medline, CAS, Google Scholar
- 90 Byrne ST, Denkin SM, Zhang Y. Aspirin antagonism in isoniazid treatment of tuberculosis in mice. Antimicrob. Agents Chemother.51(2),794–795 (2007).Crossref, Medline, CAS, Google Scholar
- 91 Hirsch CS, Yoneda T, Averill L, Ellner JJ, Toossi Z. Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-β 1. J. Infect. Dis.170(5),1229–1237 (1994).Crossref, Medline, CAS, Google Scholar
- 92 Othieno C, Hirsch CS, Hamilton BD, Wilkinson K, Ellner JJ, Toossi Z. Interaction of Mycobacterium tuberculosis-induced transforming growth factor β 1 and interleukin-10. Infect. Immun.67(11),5730–5735 (1999).Crossref, Medline, CAS, Google Scholar
- 93 Ellner JJ. Immunoregulation in TB: observations and implications. Clin. Transl. Sci.3(1),23–28 (2010).Crossref, Medline, CAS, Google Scholar
- 94 Turner J, Gonzalez-Juarrero M, Ellis DL et al.In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J. Immunol.169(11),6343–6351 (2002).Crossref, Medline, CAS, Google Scholar
- 95 Turner J, Gonzalez-Juarrero M, Saunders BM et al. Immunological basis for reactivation of tuberculosis in mice. Infect. Immun.69(5),3264–3270 (2001).Crossref, Medline, CAS, Google Scholar
- 96 Ordway D, Henao-Tamayo M, Harton M et al. The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation. J. Immunol.179(1),522–531 (2007).Crossref, Medline, CAS, Google Scholar
- 97 Hernandez-Pando R, Orozco H, Arriaga K, Sampieri A, Larriva-Sahd J, Madrid-Marina V. Analysis of the local kinetics and localization of interleukin-1α, tumour necrosis factor-α and transforming growth factor-β, during the course of experimental pulmonary tuberculosis. Immunology90(4),607–617 (1997).Crossref, Medline, CAS, Google Scholar
- 98 Beamer GL, Flaherty DK, Assogba BD et al. Interleukin-10 promotes Mycobacterium tuberculosis disease progression in CBA/J mice. J. Immunol.181(8),5545–5550 (2008).Crossref, Medline, CAS, Google Scholar
- 99 Hernandez-Pando R, Orozco-Esteves H, Maldonado HA et al. A combination of a transforming growth factor-β antagonist and an inhibitor of cyclooxygenase is an effective treatment for murine pulmonary tuberculosis. Clin. Exp. Immunol.144(2),264–272 (2006).Crossref, Medline, CAS, Google Scholar
- 100 Hirsch CS, Ellner JJ, Blinkhorn R, Toossi Z. In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor β. Proc. Natl Acad. Sci. USA94(8),3926–3931 (1997).Crossref, Medline, CAS, Google Scholar
- 101 Rosas-Taraco AG, Higgins DM, Sanchez-Campillo J, Lee EJ, Orme IM, Gonzalez-Juarrero M. Local pulmonary immunotherapy with siRNA targeting TGFβ1 enhances antimicrobial capacity in Mycobacterium tuberculosis infected mice. Tuberculosis (Edinb.)91(1),98–106 (2011).Crossref, Medline, CAS, Google Scholar
- 102 Hoff DR, Ryan GJ, Driver ER et al. Location of intra- and extracellular M. tuberculosis populations in lungs of mice and guinea pigs during disease progression and after drug treatment. PLoS ONE6(3),E17550 (2011).Crossref, Medline, CAS, Google Scholar
- 103 Gonzalez-Juarrero M, Turner OC, Turner J, Marietta P, Brooks JV, Orme IM. Temporal and spatial arrangement of lymphocytes within lung granulomas induced by aerosol infection with Mycobacterium tuberculosis. Infect. Immun.69(3),1722–1728 (2001).Crossref, Medline, CAS, Google Scholar
- 104 Turner J, Frank AA, Brooks JV, Gonzalez-Juarrero M, Orme IM. The progression of chronic tuberculosis in the mouse does not require the participation of B lymphocytes or interleukin-4. Exp. Gerontol.36(3),537–545 (2001).Crossref, Medline, CAS, Google Scholar
- 105 Glatman-Freedman A. The role of antibody-mediated immunity in defense against Mycobacterium tuberculosis: advances toward a novel vaccine strategy. Tuberculosis (Edinb.)86(3–4),191–197 (2006).Crossref, Medline, CAS, Google Scholar
- 106 Glatman-Freedman A, Casadevall A. Serum therapy for tuberculosis revisited: reappraisal of the role of antibody-mediated immunity against Mycobacterium tuberculosis. Clin. Microbiol. Rev.11(3),514–532 (1998).Crossref, Medline, CAS, Google Scholar
- 107 Rich AR. The Pathogenesis of Tuberculosis. CC Thomas, Springfield, IL, USA (1944).Google Scholar
- 108 Latham A. Caseating pulmonary tuberculosis treated by tuberculin (T.R.) and fresh horse serum, both administered by the mouth. Proc. R. Soc. Med.1(Clin. Sect.),100–104 (1908).Medline, CAS, Google Scholar
- 109 Teitelbaum R, Glatman-Freedman A, Chen B et al. A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival. Proc. Natl Acad. Sci. USA95(26),15688–15693 (1998).Crossref, Medline, CAS, Google Scholar
- 110 Glatman-Freedman A, Mednick AJ, Lendvai N, Casadevall A. Clearance and organ distribution of Mycobacterium tuberculosis lipoarabinomannan (LAM) in the presence and absence of LAM-binding immunoglobulin M. Infect. Immun.68(1),335–341 (2000).Crossref, Medline, CAS, Google Scholar
- 111 Pethe K, Alonso S, Biet F et al. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature412(6843),190–194 (2001).Crossref, Medline, CAS, Google Scholar
- 112 Hussain R, Shiratsuchi H, Ellner JJ, Wallis RS. PPD-specific IgG1 antibody subclass upregulate tumour necrosis factor expression in PPD-stimulated monocytes: possible link with disease pathogenesis in tuberculosis. Clin. Exp. Immunol.119(3),449–455 (2000).Medline, CAS, Google Scholar
- 113 Hussain R, Shiratsuchi H, Phillips M, Ellner J, Wallis RS. Opsonizing antibodies (IgG1) up-regulate monocyte proinflammatory cytokines tumour necrosis factor-α (TNF-α) and IL-6 but not anti-inflammatory cytokine IL-10 in mycobacterial antigen-stimulated monocytes-implications for pathogenesis. Clin. Exp. Immunol.123(2),210–218 (2001).Crossref, Medline, CAS, Google Scholar
- 114 Rook GA, Onyebujoh P, Wilkins E et al. A longitudinal study of per cent agalactosyl IgG in tuberculosis patients receiving chemotherapy, with or without immunotherapy. Immunology81(1),149–154 (1994).Medline, CAS, Google Scholar
- 115 Sartain MJ, Slayden RA, Singh KK, Laal S, Belisle JT. Disease state differentiation and identification of tuberculosis biomarkers via native antigen array profiling. Mol. Cell Proteomics5(11),2102–2113 (2006).Crossref, Medline, CAS, Google Scholar
- 116 Samanich K, Belisle JT, Laal S. Homogeneity of antibody responses in tuberculosis patients. Infect. Immun.69(7),4600–4609 (2001).Crossref, Medline, CAS, Google Scholar
- 117 Kunnath-Velayudhan S, Salamon H, Wang HY et al. Dynamic antibody responses to the Mycobacterium tuberculosis proteome. Proc. Natl Acad. Sci. USA107(33),14703–14708 (2010).Crossref, Medline, CAS, Google Scholar
- 118 Lyashchenko K, Colangeli R, Houde M, Al Jahdali H, Menzies D, Gennaro ML. Heterogeneous antibody responses in tuberculosis. Infect. Immun.66(8),3936–3940 (1998).Crossref, Medline, CAS, Google Scholar
- 119 Rawls KA, Grundner C, Ellman JA. Design and synthesis of nonpeptidic, small molecule inhibitors for the Mycobacterium tuberculosis protein tyrosine phosphatase PtpB. Organic Biomol. Chem.8(18),4066–4070 (2010).Crossref, Medline, CAS, Google Scholar
- 120 Ott PA, Adams S. Small-molecule protein kinase inhibitors and their effects on the immune system: implications for cancer treatment. Immunotherapy3(2),213–227 (2011).Link, CAS, Google Scholar
- 121 Lammas DA, Stober C, Harvey CJ, Kendrick N, Panchalingam S, Kumararatne DS. ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. Immunity7(3),433–444 (1997).Crossref, Medline, CAS, Google Scholar
- 122 Moisan J, Wojciechowski W, Guilbault C et al. Clearance of infection with Mycobacterium M. bovis BCG in mice is enhanced by treatment with S28463 (R-848), and its efficiency depends on expression of wild-type Nramp1 (resistance allele). Antimicrob. Agents Chemother.45(11),3059–3064 (2001).Crossref, Medline, CAS, Google Scholar
- 123 Marriott JB, Westby M, Cookson S et al. CC-3052: a water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-α production. J. Immunol.161(8),4236–4243 (1998).Medline, CAS, Google Scholar
- 124 Wehenkel A, Bellinzoni M, Grana M et al. Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential. Biochim. Biophys. Acta1784(1),193–202 (2008).Crossref, Medline, CAS, Google Scholar

