• 1
    World Health Organization. Global Tuberculosis Control 2009: Epidemiology, Strategy, Financing. WHO, Geneva, 2009.
  • 2
    World Health Organization. Anti-Tuberculosis Drug Resistance in the World: The WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance. WHO, Geneva, 2008.
  • 3
    Cooper AM. Cell-mediated immune responses in tuberculosis. Annu. Rev. Immunol. 2009; 27: 393422.
  • 4
    Hanekom WA, Abel B, Scriba TJ. Immunological protection against tuberculosis. S. Afr. Med. J. 2007; 97: 9737.
  • 5
    Reece ST, Kaufmann SH. Rational design of vaccines against tuberculosis directed by basic immunology. Int. J. Med. Microbiol. 2008; 298: 14350.
  • 6
    Dietrich J, Doherty TM. Interaction of Mycobacterium tuberculosis with the host: consequences for vaccine development. APMIS 2009; 117: 44057.
  • 7
    Grotzke JE, Lewinsohn DM. Role of CD8+ T lymphocytes in control of Mycobacterium tuberculosis infection. Microbes Infect. 2005; 7: 77688.
  • 8
    Dheda K, Smit RZ, Badri M et al. T-cell interferon-gamma release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings. Curr. Opin. Pulm. Med. 2009; 15: 188200.
  • 9
    Pai M, Kalantri S, Dheda K. New tools and emerging technologies for the diagnosis of tuberculosis: part I. Latent tuberculosis. Expert Rev. Mol. Diagn. 2006; 6: 41322.
  • 10
    Mack U, Migliori GB, Sester M et al. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur. Respir. J. 2009; 33: 95673.
  • 11
    Barry CE 3rd, Boshoff HI, Dartois V et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat. Rev. Microbiol. 2009; 7: 84555.
  • 12
    Morrison J, Pai M, Hopewell PC. Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect. Dis. 2008; 8: 35968.
  • 13
    Cobat A, Gallant CJ, Simkin L et al. Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis. J. Exp. Med. 2009; 206: 258391.
  • 14
    Schwander SK, Torres M, Carranza CC et al. Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in healthy household contacts of patients with active tuberculosis and healthy controls from the community. J. Immunol. 2000; 165: 147985.
  • 15
    Carranza C, Juarez E, Torres M et al. Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts. Am. J. Respir. Crit. Care Med. 2006; 173: 23845.
  • 16
    Pai M, Joshi R, Dogra S et al. Serial testing of health care workers for tuberculosis using interferon-gamma assay. Am. J. Respir. Crit. Care Med. 2006; 174: 34955.
  • 17
    Ewer K, Millington KA, Deeks JJ et al. Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis. Am. J. Respir. Crit. Care Med. 2006; 174: 8319.
  • 18
    Hill PC, Brookes RH, Fox A et al. Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection. PLoS Med. 2007; 4: e192.
  • 19
    Young DB, Gideon HP, Wilkinson RJ. Eliminating latent tuberculosis. Trends Microbiol. 2009; 17: 1838.
  • 20
    Pai M. Spectrum of latent tuberculosis—existing tests cannot resolve the underlying phenotypes. Nat. Rev. Microbiol. 2010; 8: 242.
  • 21
    Schlesinger LS, Bellinger-Kawahara CG, Payne NR et al. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J. Immunol. 1990; 144: 277180.
  • 22
    Tailleux L, Pham-Thi N, Bergeron-Lafaurie A et al. DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis. PLoS Med. 2005; 2: e381.
  • 23
    Kang PB, Azad AK, Torrelles JB et al. The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J. Exp. Med. 2005; 202: 98799.
  • 24
    Hirsch CS, Ellner JJ, Russell DG et al. Complement receptor-mediated uptake and tumor necrosis factor-alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol. 1994; 152: 74353.
  • 25
    Tailleux L, Schwartz O, Herrmann JL et al. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J. Exp. Med. 2003; 197: 1217.
  • 26
    Geijtenbeek TB, Van Vliet SJ, Koppel EA et al. Mycobacteria target DC-SIGN to suppress dendritic cell function. J. Exp. Med. 2003; 197: 717.
  • 27
    Schwander SK, Sada E, Torres M et al. T lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis. J. Infect. Dis. 1996; 173: 126772.
  • 28
    Robinson DS, Ying S, Taylor IK et al. Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 1994; 149: 98993.
  • 29
    Schwander SK, Torres M, Sada E et al. Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar lymphocytes during active pulmonary tuberculosis. J. Infect. Dis. 1998; 178: 143445.
  • 30
    Taha RA, Kotsimbos TC, Song YL et al. IFN-gamma and IL-12 are increased in active compared with inactive tuberculosis. Am. J. Respir. Crit. Care Med. 1997; 155: 11359.
  • 31
    Herrera MT, Torres M, Nevels D et al. Compartmentalized bronchoalveolar IFN-gamma and IL-12 response in human pulmonary tuberculosis. Tuberculosis (Edinb) 2009; 89: 3847.
  • 32
    Pieters J, Gatfield J. Hijacking the host: survival of pathogenic mycobacteria inside macrophages. Trends Microbiol. 2002; 10: 1426.
  • 33
    Young D, Hussell T, Dougan G. Chronic bacterial infections: living with unwanted guests. Nat. Immunol. 2002; 3: 102632.
  • 34
    Chua J, Vergne I, Master S et al. A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest. Curr. Opin. Microbiol. 2004; 7: 717.
  • 35
    Dahl KE, Shiratsuchi H, Hamilton BD et al. Selective induction of transforming growth factor beta in human monocytes bylipoarabinomannan of Mycobacterium tuberculosis. Infect. Immun. 1996; 64: 399405.
  • 36
    Hirsch CS, Hussain R, Toossi Z et al. Cross-modulation by transforming growth factor beta in human tuberculosis: suppression of antigen-driven blastogenesis and interferon gamma production. Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 31938.
  • 37
    Hirsch CS, Toossi Z, Othieno C et al. Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J. Infect. Dis. 1999; 180: 206973.
  • 38
    Almeida AS, Lago PM, Boechat N et al. Tuberculosis is associated with a down-modulatory lung immune response that impairs Th1-type immunity. J. Immunol. 2009; 183: 71831.
  • 39
    Kursar M, Koch M, Mittrucker HW et al. Cutting edge: regulatory T cells prevent efficient clearance of Mycobacterium tuberculosis. J. Immunol. 2007; 178: 26615.
  • 40
    Guyot-Revol V, Innes JA, Hackforth S et al. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am. J. Respir. Crit. Care Med. 2006; 173: 80310.
  • 41
    Ribeiro-Rodrigues R, Resende Co T, Rojas R et al. A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis. Clin. Exp. Immunol. 2006; 144: 2534.
  • 42
    Daley CL, Small PM, Schecter GF et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N. Engl. J. Med. 1992; 326: 2315.
  • 43
    Sonnenberg P, Murray J, Glynn JR et al. HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South African mineworkers. Lancet 2001; 358: 168793.
  • 44
    Selwyn PA, Hartel D, Lewis VA et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N. Engl. J. Med. 1989; 320: 54550.
  • 45
    Bocchino M, Sanduzzi A, Bariffi F. Mycobacterium tuberculosis and HIV co-infection in the lung: synergic immune dysregulation leading to disease progression. Monaldi Arch. Chest Dis. 2000; 55: 3818.
  • 46
    Collins KR, Mayanja-Kizza H, Sullivan BA et al. Greater diversity of HIV-1 quasispecies in HIV-infected individuals with active tuberculosis. J. Acquir. Immune Defic. Syndr. 2000; 24: 40817.
  • 47
    Keane J, Gershon S, Wise RP et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N. Engl. J. Med. 2001; 345: 1098104.
  • 48
    Wallis RS, Broder M, Wong J et al. Granulomatous infections due to tumor necrosis factor blockade: correction. Clin. Infect. Dis. 2004; 39: 12545.
  • 49
    Wallis RS. Mycobacterial disease attributable to tumor necrosis factor-alpha blockers. Clin. Infect. Dis. 2008; 47: 16035, author reply 5–6.
  • 50
    De Jong R, Altare F, Haagen IA et al. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 1998; 280: 14358.
  • 51
    Altare F, Durandy A, Lammas D et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 1998; 280: 14325.
  • 52
    Jouanguy E, Lamhamedi-Cherradi S, Lammas D et al. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat. Genet. 1999; 21: 3708.
  • 53
    Newport MJ, Huxley CM, Huston S et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 1996; 335: 19419.
  • 54
    Altare F, Jouanguy E, Lamhamedi-Cherradi S et al. A causative relationship between mutant IFNgR1 alleles and impaired cellular response to IFNgamma in a compound heterozygous child. Am. J. Hum. Genet. 1998; 62: 7236.
  • 55
    Garton NJ, Waddell SJ, Sherratt AL et al. Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Med. 2008; 5: e75.
  • 56
    Russell DG, Cardona PJ, Kim MJ et al. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat. Immunol. 2009; 10: 9438.
  • 57
    Dheda K, Booth H, Huggett JF et al. Lung remodeling in pulmonary tuberculosis. J. Infect. Dis. 2005; 192: 12019.
  • 58
    Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol. 2007; 7: 17990.
  • 59
    Ernst JD. Macrophage receptors for Mycobacterium tuberculosis. Infect. Immun. 1998; 66: 127781.
  • 60
    Ferguson JS, Martin JL, Azad AK et al. Surfactant protein D increases fusion of Mycobacterium tuberculosis-containing phagosomes with lysosomes in human macrophages. Infect. Immun. 2006; 74: 70059.
  • 61
    Divangahi M, Mostowy S, Coulombe F et al. NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J. Immunol. 2008; 181: 715765.
  • 62
    Korbel DS, Schneider BE, Schaible UE. Innate immunity in tuberculosis: myths and truth. Microbes Infect. 2008; 10: 9951004.
  • 63
    Liu PT, Modlin RL. Human macrophage host defense against Mycobacterium tuberculosis. Curr. Opin. Immunol. 2008; 20: 3716.
  • 64
    Pathak SK, Basu S, Basu KK et al. Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages. Nat. Immunol. 2007; 8: 61018.
  • 65
    Liu PT, Stenger S, Li H et al. Toll-like receptor triggering of a vitamin d-mediated human antimicrobial response. Science 2006; 311: 17703.
  • 66
    Chocano-Bedoya P, Ronnenberg AG. Vitamin D and tuberculosis. Nutr. Rev. 2009; 67: 28993.
  • 67
    Mendez-Samperio P. Role of antimicrobial peptides in host defense against mycobacterial infections. Peptides 2008; 29: 183641.
  • 68
    Liu PT, Stenger S, Tang DH et al. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J. Immunol. 2007; 179: 20603.
  • 69
    Yang CS, Shin DM, Kim KH et al. NADPH oxidase 2 interaction with TLR2 is required for efficient innate immune responses to mycobacteria via cathelicidin expression. J. Immunol. 2009; 182: 3696705.
  • 70
    Bellamy RJ, Hill AV. Host genetic susceptibility to human tuberculosis. Novartis Found. Symp. 1998; 217: 313, discussion –23.
  • 71
    Thuong NT, Hawn TR, Thwaites GE et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun. 2007; 8: 4228.
  • 72
    Verreck FA, De Boer T, Langenberg DM et al. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 45605.
  • 73
    Savage ND, De Boer T, Walburg KV et al. Human anti-inflammatory macrophages induce Foxp3+ GITR+ CD25+ regulatory T cells, which suppress via membrane-bound TGFbeta-1. J. Immunol. 2008; 181: 22206.
  • 74
    Kaufmann SH. How can immunology contribute to the control of tuberculosis? Nat. Rev. Immunol. 2001; 1: 2030.
  • 75
    MacMicking JD, North RJ, LaCourse R et al. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 1997; 94: 52438.
  • 76
    Gutierrez MG, Master SS, Singh SB et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 2004; 119: 75366.
  • 77
    Alonso S, Pethe K, Russell DG et al. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 60316.
  • 78
    Singh SB, Davis AS, Taylor GA et al. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 2006; 313: 143841.
  • 79
    MacMicking JD, Taylor GA, McKinney JD. Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science 2003; 302: 6549.
  • 80
    Harris J, De Haro SA, Master SS et al. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 2007; 27: 50517.
  • 81
    Flynn J, Chan J. Tuberculosis: latency and reactivation. Infect. Immun. 2001; 69: 4195201.
  • 82
    Bruns H, Meinken C, Schauenberg P et al. Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J. Clin. Invest. 2009; 119: 116777.
  • 83
    Sada-Ovalle I, Chiba A, Gonzales A et al. Innate invariant NKT cells recognize mycobacterium tuberculosis-infected macrophages, produce interferon-gamma, and kill intracellular bacteria. PLoS Pathog. 2008; 4: e1000239.
  • 84
    Millman AC, Salman M, Dayaram YK et al. Natural killer cells, glutathione, cytokines, and innate immunity against Mycobacterium tuberculosis. J. Interferon Cytokine Res. 2008; 28: 15365.
  • 85
    Mars LT, Araujo L, Kerschen P et al. Invariant NKT cells inhibit development of the Th17 lineage. Proc. Natl. Acad. Sci. U.S.A. 2009; 106: 623843.
  • 86
    Martineau AR, Newton SM, Wilkinson KA et al. Neutrophil-mediated innate immune resistance to mycobacteria. J. Clin. Invest. 2007; 117: 198894.
  • 87
    Soehnlein O, Weber C, Lindbom L. Neutrophil granule proteins tune monocytic cell function. Trends Immunol. 2009; 30: 53846.
  • 88
    Persson YAZ, Blomgran-Julinder R, Rahman S et al. Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria. Microbes Infect. 2008; 10: 23340.
  • 89
    Dannenberg AM. Pathogenesis of Human Pulmonary Tuberculosis: Insights from the Rabbit Model. ASM Press, Washington, DC. 2006.
  • 90
    Carlos D, Frantz FG, Souza-Junior DA et al. TLR2-dependent mast cell activation contributes to the control of Mycobacterium tuberculosis infection. Microbes Infect. 2009; 11: 7708.
  • 91
    Casetti R, Martino A. The plasticity of gamma delta T cells: innate immunity, antigen presentation and new immunotherapy. Cell Mol. Immunol. 2008; 5: 16170.
  • 92
    Martino A, Casetti R, Sacchi A et al. Central memory V gamma 9V delta 2 T lymphocytes primed and expanded by bacillus Calmette-Guerin-Infected dendritic cells kill mycobacterial-infected monocytes. J. Immunol. 2007; 179: 305764.
  • 93
    Martin B, Hirota K, Cua DJ et al. Interleukin-17-producing [gamma][delta] T cells selectively expand in response to pathogen products and environmental signals. Immunity 2009; 31: 32130.
  • 94
    Khader SA, Partida-Sanchez S, Bell G et al. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. J. Exp. Med. 2006; 203: 180515.
  • 95
    Schaible UE, Winau F, Sieling PA et al. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat. Med. 2003; 9: 103946.
  • 96
    Ngai P, McCormick S, Small C et al. Gamma interferon responses of CD4 and CD8 T-cell subsets are quantitatively different and independent of each other during pulmonary Mycobacterium bovis BCG infection. Infect. Immun. 2007; 75: 224452.
  • 97
    Kaufmann SH, McMichael AJ. Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis. Nat. Med. 2005; 11: S3344.
  • 98
    Wang J, Santosuosso M, Ngai P et al. Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. J. Immunol. 2004; 173: 45907.
  • 99
    Kaufmann SHE, Parida SK. Tuberculosis. in Africa: learning from pathogenesis for biomarker identification. Cell Host. Microbe. 2008; 4: 21928.
  • 100
    Dorhoi A, Kaufmann SHE. Fine-tuning of T cell responses during infection. Curr. Opin. Immunol. 2009; 21: 36777.
  • 101
    Trinchieri G. Regulatory role of T cells producing both interferon gamma and interleukin 10 in persistent infection. J. Exp. Med. 2001; 194: F537.
  • 102
    Joosten SA, Ottenhoff TH. Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum. Immunol. 2008; 69: 76070.
  • 103
    Scott-Browne JP, Shafiani S, Tucker-Heard G et al. Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J. Exp. Med. 2007; 204: 215969.
  • 104
    Li L, Wu CY. CD4(+)CD25(+) Treg cells inhibit human memory gamma delta T cells to produce IFN-gamma in response to M tuberculosis antigen ESAT-6. Blood 2008; 111: 562936.
  • 105
    Gong G, Shao L, Wang Y et al. Phosphoantigen-activated V gamma 2V delta 2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection. Blood 2009; 113: 83745.
  • 106
    Sharma PK, Saha PK, Singh A et al. FoxP3(+) regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis. Am. J. Respir. Crit. Care Med. 2009; 179: 106170.
  • 107
    Rahman S, Gudetta B, Fink J et al. Compartmentalization of immune responses in human tuberculosis few CD8 + effector t cells but elevated levels of FbxP3 + regulatory T cells in the granulomatous lesions. Am. J. Pathol. 2009; 174: 221124.
  • 108
    Chiacchio T, Casetti R, Butera O et al. Characterization of regulatory T cells identified as CD4(+)CD25(high)CD39(+) in patients with active tuberculosis. Clin. Exp. Immunol. 2009; 156: 46370.
  • 109
    Jaron B, Maranghi E, Leclerc C et al. Effect of attenuation of treg during BCG immunization on anti-mycobacterial Th1 responses and protection against Mycobacterium tuberculosis. PLoS ONE 2008; 3: e2833.
  • 110
    Bayry J, Tchilian EZ, Davies MN et al. In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination. Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 102216.
  • 111
    Bettelli E, Carrier YJ, Gao WD et al. Reciprocal developmental pathways for the generation of pathogenic effector T(H)17 and regulatory T cells. Nature 2006; 441: 2358.
  • 112
    Abebe F, Bjune G. The protective role of antibody responses during Mycobacterium tuberculosis infection. Clin. Exp. Immunol. 2009; 157: 23543.
  • 113
    Maglione PJ, Chan J. How B cells shape the immune response against Mycobacterium tuberculosis. Eur. J. Immunol. 2009; 39: 67686.
  • 114
    Carroll MV, Lack N, Sim E et al. Multiple routes of complement activation by Mycobacterium bovis BCG. Mol. Immunol. 2009; 46: 336778.
  • 115
    Lindenstrom T, Agger EM, Korsholm KS et al. Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells. J. Immunol. 2009; 182: 804755.
  • 116
    Rook GA, Lowrie DB, Hernandez-Pando R. Immunotherapeutics for tuberculosis in experimental animals: is there a common pathway activated by effective protocols? J. Infect. Dis. 2007; 196: 1918.
  • 117
    Rook GA, Dheda K, Zumla A. Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not. Tuberculosis (Edinb) 2006; 86: 15262.
  • 118
    Rook GA, Dheda K, Zumla A. Immune responses to tuberculosis in developing countries: implications for new vaccines. Nat. Rev. Immunol. 2005; 5: 6617.
  • 119
    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. 2003; 168: 18591.
  • 120
    Suarez-Mendez R, Garcia-Garcia I, Fernandez-Olivera N et al. Adjuvant interferon gamma in patients with drug—resistant pulmonary tuberculosis: a pilot study. BMC Infect. Dis. 2004; 4: 44.
  • 121
    Koh WJ, Kwon OJ, Suh GY et al. Six-month therapy with aerosolized interferon-gamma for refractory multidrug-resistant pulmonary tuberculosis. J. Korean Med. Sci. 2004; 19: 16771.
  • 122
    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. 2005; 191: 85665.
  • 123
    Tramontana JM, Utaipat U, Molloy A et al. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol. Med. 1995; 1: 38497.
  • 124
    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. AIDS 2004; 18: 25764.
  • 125
    Churchyard GJ, Kaplan G, Fallows D et al. Advances in Immunotherapy for tuberculosis treatment. Clin. Chest Med. 2009; 30: 76982.
  • 126
    World Health Organization. Report of the expert consultation on immunotherapeutic interventions for tuberculosis. Geneva, 29–31 January 2007. [Accessed October 2009.] Available from URL:
  • 127
    Zuany-Amorim C, Sawicka E, Manlius C et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat. Med. 2002; 8: 6259.
  • 128
    Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Durban Immunotherapy Trial Group. Lancet 1999; 354: 11619.
  • 129
    Johnson JL, Kamya RM, Okwera A et al. Randomized controlled trial of Mycobacterium vaccaeimmunotherapy in non-human immunodeficiency virus-infected Ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration. J. Infect. Dis. 2000; 181: 130412.
  • 130
    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. Lancet 2002; 360: 10505.
  • 131
    Fan MCX, Wang K, Mao H et al. Adjuvant effect of Mycobacterium vaccae on treatment of recurrent treated pulmonary tuberculosis: a meta-analysis. Chin. J. Evid. Based Med. 2007; 7: 44955.
  • 132
    Von Reyn CF, Arbeit RD, Mtei L et al. [PS- 81689-20] The DarDar prime-boost TB vaccine trial in HIV infection: final results. Int. J. Tuberc. Lung Dis. 2008; 12: S318.
  • 133
    Roy E, Stavropoulos E, Brennan J et al. Therapeutic efficacy of high-dose intravenous immunoglobulin in Mycobacterium tuberculosis infection in mice. Infect. Immun. 2005; 73: 61019.
  • 134
    Nikolaeva LG, Maystat TV, Pylypchuk VS et al. Cytokine profiles of HIV patients with pulmonary tuberculosis resulting from adjunct immunotherapy with herbal phytoconcentrates Dzherelo and Anemin. Cytokine 2008; 44: 3926.
  • 135
    Nikolaeva LG, Maystat TV, Pylypchuk VS et al. Effect of oral immunomodulator Dzherelo in TB/HIV co-infected patients receiving anti-tuberculosis therapy under DOTS. Int. Immunopharmacol. 2008; 8: 84551.
  • 136
    Prihoda ND, Arjanova OV, Yurchenko LV et al. Adjunct immunotherapy of tuberculosis in drug-resistant TB and TB/HIV co-infected patients. Int. J. Biomed. Pharm. Sci. 2008; 2: 5964.
  • 137
    Patel N, Deshpande MM, Shah M. Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis. J. Indian Med. Assoc. 2002; 100: 1913.
  • 138
    Lowrie DB, Tascon RE, Bonato VL et al. Therapy of tuberculosis in mice by DNA vaccination. Nature 1999; 400: 26971.
  • 139
    Stickney DR, Noveljic Z, Garsd A et al. Safety and activity of the immune modulator HE2000 on the incidence of tuberculosis and other opportunistic infections in AIDS patients. Antimicrob. Agents Chemother. 2007; 51: 263941.
  • 140
    Cardona PJ, Amat I, Gordillo S et al. Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis. Vaccine 2005; 23: 13938.
  • 141
    Davies GR, Khoo SH, Aarons LJ. Optimal sampling strategies for early pharmacodynamic measures in tuberculosis. J. Antimicrob. Chemother. 2006; 58: 594600.
  • 142
    Biglino A, Crivelli P, Concialdi E et al. Clinical usefulness of ELISPOT assay on pericardial fluid in a case of suspected tuberculous pericarditis. Infection 2008; 36: 6014.
  • 143
    Mitchison DA. Assessment of new sterilizing drugs for treating pulmonary tuberculosis by culture at 2 months. Am. Rev. Respir. Dis. 1993; 147: 10623.
  • 144
    Wallis RS, Doherty TM, Onyebujoh P et al. Biomarkers for tuberculosis disease activity, cure, and relapse. Lancet Infect. Dis. 2009; 9: 16272.
  • 145
    Doherty M, Wallis RS, Zumla A. et al. Biomarkers for tuberculosis disease status and diagnosis. Curr. Opin. Pulm. Med. 2009; 15: 1817. 10.1097/MCP.0b013e328326f42c.
  • 146
    Talat N, Shahid F, Dawood G et al. Changes in biomarker profiles associated with clinical and subclinical tuberculosis in a high transmission setting: a four-year follow-up study. Scand. J. Immunol. 2009; 69: 53746.
  • 147
    Aiken AM, Hill PC, Fox A et al. Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases. BMC Infect. Dis. 2006; 6: 66.
  • 148
    Goletti D, Carrara S, Mayanja-Kizza H et al. Response to M. tuberculosis selected RD1 peptides in Ugandan HIV-infected patients with smear positive pulmonary tuberculosis: a pilot study. BMC Infect. Dis. 2008; 8: 11.
  • 149
    Carrara S, Vincenti D, Petrosillo N et al. Use of a T cell-based assay for monitoring efficacy of antituberculosis therapy. Clin. Infect. Dis. 2004; 38: 7546.
  • 150
    Siawaya JF, Bapela NB, Ronacher K et al. Differential expression of interleukin-4 (IL-4) and IL-4 delta 2 mRNA, but not transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, gamma interferon, T-bet, or GATA-3 mRNA, in patients with fast and slow responses to antituberculosis treatment. Clin. Vaccine Immunol. 2008; 15: 116570.
  • 151
    Pai M, Joshi R, Bandyopadhyay M et al. Sensitivity of a whole-blood interferon-gamma assay among patients with pulmonary tuberculosis and variations in T-cell responses during anti-tuberculosis treatment. Infection 2007; 35: 98103.
  • 152
    Higuchi K, Harada N, Mori T. Interferon-gamma responses after isoniazid chemotherapy for latent tuberculosis. Respirology 2008; 13: 46872.
  • 153
    Van Zyl-Smit RN, Pai M, Peprah K et al. Within-subject variability and boosting of T cell IFN-{gamma} responses following tuberculin skin testing. Am. J. Respir. Crit. Care Med. 2009; 180: 4958.
  • 154
    Wu B, Huang C, Kato-Maeda M et al. Messenger RNA expression of IL-8, FOXP3, and IL-12beta differentiates latent tuberculosis infection from disease. J. Immunol. 2007; 178: 368894.
  • 155
    Veenstra H, Baumann R, Carroll NM et al. Changes in leucocyte and lymphocyte subsets during tuberculosis treatment; prominence of CD3dimCD56+ natural killer T cells in fast treatment responders. Clin. Exp. Immunol. 2006; 145: 25260.
  • 156
    Mukae H, Ashitani J, Tokojima M et al. Elevated levels of circulating adhesion molecules in patients with active pulmonary tuberculosis. Respirology 2003; 8: 32631.
  • 157
    Tsao TC, Hong J, Li LF et al. Imbalances between tumor necrosis factor-alpha and its soluble receptor forms, and interleukin-1beta and interleukin-1 receptor antagonist in BAL fluid of cavitary pulmonary tuberculosis. Chest 2000; 117: 1039.
  • 158
    Immanuel C, Rajeswari R, Rahman F et al. Serial evaluation of serum neopterin in HIV seronegative patients treated for tuberculosis. Int. J. Tuberc. Lung Dis. 2001; 5: 18590.
  • 159
    Bajaj G, Rattan A, Ahmad P. Prognostic value of ‘C’ reactive protein in tuberculosis. Indian Pediatr. 1989; 26: 101013.
  • 160
    Djoba Siawaya JF, Chegou NN, Van Den Heuvel MM et al. Differential cytokine/chemokines and KL-6 profiles in patients with different forms of tuberculosis. Cytokine 2009; 47: 1326.
  • 161
    Chegou NN, Black GF, Kidd M et al. Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report. BMC Pulm. Med. 2009; 9: 21.
  • 162
    Djoba Siawaya JF, Beyers N, Van Helden P et al. Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis. Clin. Exp. Immunol. 2009; 156: 6977.
  • 163
    Torres M, Herrera T, Villareal H et al. Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to the 30-kilodalton antigen of Mycobacterium tuberculosis. Infect. Immun. 1998; 66: 17680.
  • 164
    Demissie A, Ravn P, Olobo J et al. T-cell recognition of Mycobacterium tuberculosis culture filtrate fractions in tuberculosis patients and their household contacts. Infect. Immun. 1999; 67: 596771.
  • 165
    Vekemans J, Lienhardt C, Sillah JS et al. Tuberculosis contacts but not patients have higher gamma interferon responses to ESAT-6 than do community controls in The Gambia. Infect. Immun. 2001; 69: 65547.
  • 166
    Andersen P, Doherty TM. The success and failure of BCG—implications for a novel tuberculosis vaccine. Nat. Rev. Microbiol. 2005; 3: 65662.
  • 167
    Lotte A, Wasz-Hockert O, Poisson N et al. A bibliography of the complications of BCG vaccination. A comprehensive list of the world literature since the introduction of BCG up to July 1982, supplemented by over 100 personal communications. Adv. Tuberc. Res. 1984; 21: 194245.
  • 168
    Hesseling AC, Cotton MF, Fordham RC et al. Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants. Int. J. Tuberc. Lung Dis. 2008; 12: 13769.
  • 169
    Behr MA, Wilson MA, Gill WP et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 1999; 284: 15203.
  • 170
    Rieder HL. BCG vaccination. In: Davies P, BarnesP, GordonS (eds.) Clinical Tuberculosis Fourth Edition, Hodder Arnold, London, 2008; 41127.
  • 171
    Fine PE, Floyd S, Stanford JL et al. Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy. Epidemiol. Infect. 2001; 126: 37987.
  • 172
    Fine PE. BCG: the challenge continues. Scand. J. Infect. Dis. 2001; 33: 2435.
  • 173
    Elias D, Britton S, Aseffa A et al. Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-beta production. Vaccine 2008; 26: 3897902.
  • 174
    Elias D, Wolday D, Akuffo H et al. Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guerin (BCG) vaccination. Clin. Exp. Immunol. 2001; 123: 21925.
  • 175
    Resende CT, Hirsch CS, Toossi Z et al. Intestinal helminth co-infection has a negative impact on both anti-Mycobacterium tuberculosis immunity and clinical response to tuberculosis therapy. Clin. Exp. Immunol. 2007; 147: 21925.
  • 176
    Malhotra I, Mungai P, Wamachi A et al. Helminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J. Immunol. 1999; 162: 68438.
  • 177
    Guwatudde D, Nakakeeto M, Jones-Lopez EC et al. Tuberculosis in household contacts of infectious cases in Kampala, Uganda. Am. J. Epidemiol. 2003; 158: 88798.
  • 178
    Soysal A, Millington KA, Bakir M et al. Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet 2005; 366: 144351.
  • 179
    World Health Organization. Revised BCG vaccination guidelines for infants at risk for HIV infection. Wkly. Epidemiol. Rec. 2007; 82: 1936.
  • 180
    Grode L, Seiler P, Baumann S et al. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin. J. Clin. Invest. 2005; 115: 24729.
  • 181
    Horwitz MA, Harth G, Dillon BJ et al. Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc. Natl. Acad. Sci. U.S.A. 2000; 97: 138538.
  • 182
    Horwitz MA, Harth G, Dillon BJ et al. Enhancing the protective efficacy of Mycobacterium bovis BCG vaccination against tuberculosis by boosting with the Mycobacterium tuberculosis major secretory protein. Infect. Immun. 2005; 73: 467683.
  • 183
    Hess J, Miko D, Catic A et al. Mycobacterium bovis Bacille Calmette-Guerin strains secreting listeriolysin of Listeria monocytogenes. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 5299304.
  • 184
    Sun R, Skeiky YA, Izzo A et al. Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis. Vaccine 2009; 27: 441223.
  • 185
    Ibanga HB, Brookes RH, Hill PC et al. Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design. Lancet Infect. Dis. 2006; 6: 5228.
  • 186
    McShane H, Pathan AA, Sander CR et al. Boosting BCG with MVA85A: the first candidate subunit vaccine for tuberculosis in clinical trials. Tuberculosis (Edinb) 2005; 85: 4752.
  • 187
    Dietrich J, Aagaard C, Leah R et al. Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy. J. Immunol. 2005; 174: 63329.
  • 188
    Barker LF, Brennan MJ, Rosenstein PK et al. Tuberculosis vaccine research: the impact of immunology. Curr. Opin. Immunol. 2009; 21: 3318.
  • 189
    Mansoor N, Scriba TJ, De Kock M et al. HIV-1 infection in infants severely impairs the immune response induced by Bacille Calmette-Guerin vaccine. J. Infect. Dis. 2009; 199: 98290.
  • 190
    Tristao-Sa R, Ribeiro-Rodrigues R, Johnson LT et al. Intestinal nematodes and pulmonary tuberculosis. Rev. Soc. Bras. Med. Trop. 2002; 35: 5335.
  • 191
    Soares AP, Scriba TJ, Joseph S et al. Bacillus Calmette-Guerin vaccination of human newborns induces T cells with complex cytokine and phenotypic profiles. J. Immunol. 2008; 180: 356977.
  • 192
    Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat. Rev. Immunol. 2008; 8: 24758.
  • 193
    Sarrazin H, Wilkinson KA, Andersson J et al. Association between tuberculin skin test reactivity, the memory CD4 cell subset, and circulating FoxP3-expressing cells in HIV-infected persons. J. Infect. Dis. 2009; 199: 70210.
  • 194
    Vukmanovic-Stejic M, Agius E, Booth N et al. The kinetics of CD4+Foxp3+ T cell accumulation during a human cutaneous antigen-specific memory response in vivo. J. Clin. Invest. 2008; 118: 363950.
  • 195
    Dheda K, Udwadia ZF, Huggett JF et al. Utility of the antigen-specific interferon-gamma assay for the management of tuberculosis. Curr. Opin. Pulm. Med. 2005; 11: 195202.
  • 196
    Cosmi L, Maggi L, Santarlasci V et al. Detection by flow cytometry of ESAT-6- and PPD-specific circulating CD4+ T lymphocytes as a diagnostic tool for tuberculosis. Int. Arch. Allergy Immunol. 2007; 143: 19.
  • 197
    Hougardy JM, Schepers K, Place S et al. Heparin-binding-hemagglutinin-induced IFN-gamma release as a diagnostic tool for latent tuberculosis. PLoS ONE 2007; 2: e926.
  • 198
    Jafari C, Thijsen S, Sotgiu G et al. Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a tuberculosis network European trialsgroup study. Am. J. Respir. Crit. Care Med. 2009; 180: 66673.
  • 199
    Dheda K, Van Zyl-Smit RN, Meldau R et al. Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis. Thorax 2009; 64: 84753.
  • 200
    Cashmore T, Van Zyl-Smit RN, Dheda K et al. Feasibility and diagnostic utility of antigen-specific ifn-γ responses for the rapid immunodiagnosis of tb using induced sputum. (Abstract) 2nd International IGRA Symposium, Dubrovnik; 2009.
  • 201
    Dheda K, Van Zyl-Smit RN, Sechi LA et al. Utility of quantitative T cell responses versus unstimulated IFN-{gamma} for the diagnosis of pleural tuberculosis. Eur. Respir. J. 2009; 34: 111826.
  • 202
    Thomas MM, Hinks TS, Raghuraman S et al. Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells. Int. J. Tuberc. Lung Dis. 2008; 12: 6517.
  • 203
    Kosters K, Nau R, Bossink A et al. Rapid diagnosis of CNS tuberculosis by a T-cell interferon-gamma release assay on cerebrospinal fluid mononuclear cells. Infection 2008; 36: 597600.
  • 204
    Kim SH, Chu K, Choi SJ et al. Diagnosis of central nervous system tuberculosis by T-cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells. Clin. Vaccine Immunol. 2008; 15: 135662.
  • 205
    Van Zyl-Smit RN, Patel V, Dheda K et al. Rapid site-specific immunodiagnosis of tuberculosis: is it useful in clinical practice in South Africa? (Abstract) 2nd International IGRA Symposium, Dubrovnik; 2009.
  • 206
    Kim S-H, Cho O-H, Park SJ et al. Diagnosis of abdominal tuberculosis by T-cell-based assays on peripheral blood and peritoneal fluid mononuclear cells. J. Infect. 2009; 59: 40915.
  • 207
    Tinelli A, Malvasi A, Vergara D et al. Abdominopelvic tuberculosis in gynaecology: laparoscopical and new laboratory findings. Aust. N. Z. J. Obstet. Gynaecol. 2008; 48: 905.
  • 208
    Comstock GW. Tuberculosis in twins: a re-analysis of the Prophit survey. Am. Rev. Respir. Dis. 1978; 117: 6214.
  • 209
    Grzybowski S, Barnett GD, Styblo K. Contacts of cases of active pulmonary tuberculosis. Bull. Int. Union Tuberc. 1975; 50: 90106.
  • 210
    Mazurek GH, Jereb J, Lobue P et al. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm. Rep. 2005; 54: 4955.
  • 211
    Baba K, Sornes S, Hoosen AA et al. Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON TB-Gold interferon-gamma assay. BMC Infect. Dis. 2008; 8: 35.
  • 212
    Chegou NN, Walzl G, Bolliger CT et al. Evaluation of adapted whole-blood interferon-gamma release assays for the diagnosis of pleural tuberculosis. Respiration 2008; 76: 1318.
  • 213
    Losi M, Bossink A, Codecasa L et al. Use of a T-cell interferon-gamma release assay for the diagnosis of tuberculous pleurisy. Eur. Respir. J. 2007; 30: 11739.
  • 214
    Patel V, Singh R, Connolly C et al. Cerebrospinal T cell responses aid the diagnosis of tuberculous meningitis in a HIV and TB endemic population. AJRCCM 2010 (in press).
  • 215
    Locht C, Hougardy JM, Rouanet C et al. Heparin-binding hemagglutinin, from an extrapulmonary dissemination factor to a powerful diagnostic and protective antigen against tuberculosis. Tuberculosis (Edinb) 2006; 86: 3039.
  • 216
    Ruhwald M, Bjerregaard-Andersen M, Rabna P et al. IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay. BMC Res. Notes 2009; 2: 19.