Human lung immunity against Mycobacterium tuberculosis: Insights into pathogenesis and protection

American Journal of Respiratory and Critical Care Medicine

Volumn 183, Issue 6, 2011, Pages 696-707

  Schwander, Stephan ^a,b   Dheda, Keertan ^c,d,e  

^a University of Medicine   (United States)

^b RUTGERS SCHOOL OF PUBLIC HEALTH   (United States)

^c UNIVERSITY OF CAPE TOWN   (South Africa)

^d UNIVERSITY OF CAPE TOWN   (South Africa)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Alveolar macrophages; Bronchoalveolar lavage; Innate immunity; Interferon gamma release assays; Tuberculosis

Indexed keywords

BIOLOGICAL MARKER;

ADAPTIVE IMMUNITY; BACTERIAL IMMUNITY; DISEASE COURSE; HELPER CELL; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOPATHOGENESIS; INNATE IMMUNITY; LUNG ALVEOLUS; LUNG LAVAGE; LUNG TUBERCULOSIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW;

BIOLOGICAL MARKERS; BRONCHOALVEOLAR LAVAGE FLUID; DISEASE PROGRESSION; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, INNATE; LUNG; MYCOBACTERIUM TUBERCULOSIS; TUBERCULOSIS, PULMONARY;

EID: 79952732234     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201006-0963PP     Document Type: Review

References (117)

1. Dye C, Williams BG. The population dynamics and control of tuberculosis. Science 2010;328:856-861.
2. Dheda K, Shean K, Zumla A, Badri M, Streicher EM, Page-Shipp L, Willcox P, John MA, Reubenson G, Govindasamy D, et al. Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study. Lancet 2010;375:1798-1807.
3. Shenoi SV, Escombe AR, Friedland G. Transmission of drug-susceptible and drug-resistant tuberculosis and the critical importance of airborne infection control in the era of HIV infection and highly active antiretroviral therapy rollouts. Clin Infect Dis 2010;50:S231-S237.
4. Carranza C, Juarez E, Torres M, Ellner JJ, Sada E, Schwander SK. Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts. Am J Respir Crit Care Med 2005;173:238-245. (Pubitemid 43187898)
5. Schwander SK, Torres M, Carranza CC, Escobedo D, Tary-Lehmann M, Anderson P, Toossi Z, Ellner JJ, Rich EA, Sada E. 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;165:1479-1485. (Pubitemid 30604581)
6. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med 2001;345:1098-1104.
7. Fennelly KP, Martyny JW, Fulton KE, Orme IM, Cave DM, Heifets LB. Cough-generated aerosols of Mycobacterium tuberculosis: a new method to study infectiousness. Am J Respir Crit Care Med 2004;169:604-609. (Pubitemid 38270896)
8. Bates JH. Transmission and pathogenesis of tuberculosis. Clin Chest Med 1980;1:167-174. (Pubitemid 12065230)
9. Loudon RG, Bumgarner LR, Lacy J, Coffman GK. Aerial transmission of mycobacteria. Am Rev Respir Dis 1969;100:165-171.
10. Reed MB, Domenech P, Manca C, Su H, Barczak AK, Kreiswirth BN, Kaplan G, Barry CE III. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 2004;431:84-87. (Pubitemid 39215112)
11. Manca C, Tsenova L, Barry CE, Bergtold A, Freeman S, Haslett PA, Musser JM, Freedman VH, Kaplan G. Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates. J Immunol 1999;162:6740-6746. (Pubitemid 29309400)
12. Sinsimer D, Huet G, Manca C, Tsenova L, Koo MS, Kurepina N, Kana B, Mathema B, Marras SA, Kreiswirth BN, et al. The phenolic glycolipid of Mycobacterium tuberculosis differentially modulates the early host cytokine response but does not in itself confer hypervirulence. Infect Immun 2008;76:3027-3036.
13. Manca C, Tsenova L, Freeman S, Barczak AK, Tovey M, Murray PJ, Barry C, Kaplan G. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway. J Interferon Cytokine Res 2005;25:694-701. (Pubitemid 43010524)
14. Zhang M, Gong J, Yang Z, Samten B, Cave MD, Barnes PF. Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in human macrophages. J Infect Dis 1999;179:1213-1217. (Pubitemid 29196503)
15. Dheda K, Schwander SK, Zhu B, van Zyl-Smit RN, Zhang Y. The immunology of tuberculosis: from bench to bedside. Respirology 2010;15:433-450.
16. Barry CE III, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, Schnappinger D, Wilkinson RJ, Young D. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 2009;7:845-855.
17. Holt PG, Strickland DH, Wikstrom ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol 2008;8:142-152. (Pubitemid 351161302)
18. Hirsch CS, Ellner JJ, Russell DG, Rich EA. Complement receptor-mediated uptake and tumor necrosis factor-α-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J Immunol 1994;152:743-753. (Pubitemid 24072978)
19. Sadek MI, Sada E, Toossi Z, Schwander SK, Rich EA. Chemokines induced by infection of mononuclear phagocytes with mycobacteria and present in lung alveoli during active pulmonary tuberculosis. Am J Respir Cell Mol Biol 1998;19:513-521. (Pubitemid 128354222)
20. Laviolette M. Lymphocyte fluctuation in bronchoalveolar lavage fluid in normal volunteers. Thorax 1985;40:651-656.
21. Merchant RK, Schwartz DA, Helmers RA, Dayton CS, Hunninghake GW. Bronchoalveolar lavage cellularity: the distribution in normal volunteers. Am Rev Respir Dis 1992;146:448-453.
22. Ettensohn DB, Jankowski MJ, Duncan PG, Lalor PA. Bronchoalveolar lavage in the normal volunteer subject. I. Technical aspects and intersubject variability. Chest 1988;94:275-280.
23. Hunninghake GW, Gadek JE, Kawanami O, Ferrans VJ, Crystal RG. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. Am J Pathol 1979;97:149-206.
24. Reynolds HY, Fulmer JD, Kazmierowski JA, Roberts WC, Frank MM, Crystal RG. Analysis of cellular and protein content of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. J Clin Invest 1977;59:165-175. (Pubitemid 8018052)
25. Lommatzsch M, Bratke K, Bier A, Julius P, Kuepper M, Luttmann W, Virchow JC. Airway dendritic cell phenotypes in inflammatory diseases of the human lung. Eur Respir J 2007;30:878-886. (Pubitemid 351194790)
26. Jafari C, Thijsen S, Sotgiu G, Goletti D, Benitez JA, Losi M, Eberhardt R, Kirsten D, Kalsdorf B, Bossink A, et al. Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials Group study. Am J Respir Crit Care Med 2009;180:666-673.
27. Song K, Bolton DL, Wilson RL, Camp JV, Bao S, Mattapallil JJ, Herzenberg LA, Herzenberg LA, Andrews CA, Sadoff JC, et al. Genetic immunization in the lung induces potent local and systemic immune responses. Proc Natl Acad Sci USA 2010;107:22213-22218.
28. Schwander SK, Torres M, Sada E, Carranza C, Ramos E, Tary-Lehmann M, Wallis RS, Sierra J, Rich EA. Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar lymphocytes during active pulmonary tuberculosis. J Infect Dis 1998;178:1434-1445.
29. Hirsch CS, Toossi Z, Othieno C, Johnson JL, Schwander SK, Robertson S, Wallis RS, Edmonds K, Okwera A, Mugerwa R, et al. Depressed T-cell interferon-γ responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J Infect Dis 1999;180:2069-2073.
30. Schwander SK, Sada E, Torres M, Escobedo D, Sierra JG, Alt S, Rich EA. T lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis. J Infect Dis 1996;173:1267-1272. (Pubitemid 26251475)
31. Herrera MT, Torres M, Nevels D, Perez-Redondo CN, Ellner JJ, Sada E, Schwander SK. Compartmentalized bronchoalveolar IFN-γ and IL-12 response in human pulmonary tuberculosis. Tuberculosis (Edinb) 2009;89:38-47.
32. Robinson DS, Ying S, Taylor IK, Wangoo A, Mitchell DM, Kay AB, Hamid Q, Shaw RJ. Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-γ gene activation in pulmonary tuberculosis. Am J Respir Crit Care Med 1994;149:989-993. (Pubitemid 24108493)
33. Law KF, Jagirdar J, Weiden MD, Bodkin M, Rom WN. Tuberculosis in HIV-positive patients: cellular response and immune activation in the lung. Am J Respir Crit Care Med 1996;153:1377-1384. (Pubitemid 26112605)
34. Fletcher HA, Owiafe P, Jeffries D, Hill P, Rook GA, Zumla A, Doherty TM, Brookes RH. Increased expression of mRNA encoding interleukin (IL)-4 and its splice variant IL-4δ2 in cells from contacts of Mycobacterium tuberculosis, in the absence of in vitro stimulation. Immunology 2004;112:669-673. (Pubitemid 39061493)
35. Dheda K, Chang JS, Breen RA, Haddock JA, Lipman MC, Kim LU, Huggett JF, Johnson MA, Rook GA, Zumla A. Expression of a novel cytokine, IL-4δ2, in HIV and HIV-tuberculosis co-infection. AIDS 2005;19:1601-1606. (Pubitemid 41502672)
36. Almeida AS, Lago PM, Boechat N, Huard RC, Lazzarini LC, Santos AR, Nociari M, Zhu H, Perez-Sweeney BM, Bang H, et al. Tuberculosis is associated with a down-modulatory lung immune response that impairs Th1-type immunity. J Immunol 2009;183:718-731.
37. 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;8:359-368.
38. Bermudez LE, Goodman J. Mycobacterium tuberculosis invades and replicates within type II alveolar cells. Infect Immun 1996;64:1400-1406. (Pubitemid 26102407)
39. Eum SY, Kong JH, Hong MS, Lee YJ, Kim JH, Hwang SH, Cho SN, Via LE, Barry CE III. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB. Chest 2010;137:122-128.
40. Faldt J, Dahlgren C, Karlsson A, Ahmed AM, Minnikin DE, Ridell M. Activation of human neutrophils by mycobacterial phenolic glycolipids. Clin Exp Immunol 1999;118:253-260. (Pubitemid 29519256)
41. Neufert C, Pai RK, Noss EH, Berger M, Boom WH, Harding CV. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation. J Immunol 2001;167:1542-1549. (Pubitemid 32703154)
42. Korbel DS, Schneider BE, Schaible UE. Innate immunity in tuberculosis: myths and truth. Microbes Infect 2008;10:995-1004.
43. Kisich KO, Higgins M, Diamond G, Heifets L. Tumor necrosis factor α stimulates killing of Mycobacterium tuberculosis by human neutrophils. Infect Immun 2002;70:4591-4599. (Pubitemid 34790972)
44. Martineau AR, Newton SM, Wilkinson KA, Kampmann B, Hall BM, Nawroly N, Packe GE, Davidson RN, Griffiths CJ, Wilkinson RJ. Neutrophil-mediated innate immune resistance to mycobacteria. J Clin Invest 2007;117:1988-1994. (Pubitemid 47036333)
45. Persson YA, Blomgran-Julinder R, Rahman S, Zheng L, Stendahl O. 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;10:233-240.
46. Tan BH, Meinken C, Bastian M, Bruns H, Legaspi A, Ochoa MT, Krutzik SR, Bloom BR, Ganz T, Modlin RL, et al. Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens. J Immunol 2006;177:1864-1871. (Pubitemid 44092525)
47. Liu PT, Modlin RL. Human macrophage host defense against Mycobacterium tuberculosis. Curr Opin Immunol 2008;20:371-376.
48. Bulut Y, Michelsen KS, Hayrapetian L, Naiki Y, Spallek R, Singh M, Arditi M. Mycobacterium tuberculosis heat shock proteins use diverse Toll-like receptor pathways to activate pro-inflammatory signals. J Biol Chem 2005;280:20961-20967. (Pubitemid 40805653)
49. Reiling N, Holscher C, Fehrenbach A, Kroger S, Kirschning CJ, Goyert S, Ehlers S. Cutting edge: Toll-like receptor (TLR)2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol 2002;169:3480-3484.
50. Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A, Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J Exp Med 2005;202:1715-1724. (Pubitemid 41815877)
51. Pompei L, Jang S, Zamlynny B, Ravikumar S, McBride A, Hickman SP, Salgame P. Disparity in IL-12 release in dendritic cells and macrophages in response to Mycobacterium tuberculosis is due to use of distinct TLRs. J Immunol 2007;178:5192-5199. (Pubitemid 46595303)
52. Rivas-Santiago B, Schwander SK, Sarabia C, Diamond G, Klein-Patel ME, Hernandez-Pando R, Ellner JJ, Sada E. Human β-defensin 2 is expressed and associated with Mycobacterium tuberculosis during infection of human alveolar epithelial cells. Infect Immun 2005;73:4505-4511. (Pubitemid 41105604)
53. Doz E, Rose S, Court N, Front S, Vasseur V, Charron S, GilleronM, Puzo G, Fremaux I, Delneste Y, et al. Mycobacterial phosphatidylinositol mannosides negatively regulate host Toll-like receptor 4, MyD88-dependent proinflammatory cytokines, and TRIF-dependent costimulatory molecule expression. J Biol Chem 2009;284:23187-23196.
54. Pathak SK, Basu S, Basu KK, Banerjee A, Pathak S, Bhattacharyya A, Kaisho T, Kundu M, Basu J. Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages. Nat Immunol 2007;8:610-618. (Pubitemid 46785125)
55. Pai RK, Convery M, Hamilton TA, Boom WH, Harding CV. Inhibition of IFN-γ-induced class II transactivator expression by a 19-kDa lipoprotein from Mycobacterium tuberculosis: a potential mechanism for immune evasion. J Immunol 2003;171:175-184. (Pubitemid 36745286)
56. Noss EH, Pai RK, Sellati TJ, Radolf JD, Belisle J, Golenbock DT, Boom WH, Harding CV. Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J Immunol 2001;167:910-918. (Pubitemid 32660847)
57. Harding CV, Boom WH. Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat Rev Microbiol 2010;8:296-307.
58. Deretic V, Delgado M, Vergne I, Master S, De HS, Ponpuak M, Singh S. Autophagy in immunity against Mycobacterium tuberculosis: a model system to dissect immunological roles of autophagy. Curr Top Microbiol Immunol 2009;335:169-188.
59. Kumar D, Nath L, Kamal MA, Varshney A, Jain A, Singh S, Rao KV. Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell 2010;140:731-743.
60. Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 2006;313:1438-1441. (Pubitemid 44360272)
61. Juarez E, Nunez C, Sada E, Ellner JJ, Schwander SK, Torres M. Differential expression of Toll-like receptors on human alveolar macrophages and autologous peripheral monocytes. Respir Res 2010;11:2.
62. Henning LN, Azad AK, Parsa KV, Crowther JE, Tridandapani S, Schlesinger LS. Pulmonary surfactant protein A regulates TLR expression and activity in human macrophages. J Immunol 2008;180:7847-7858.
63. Ferguson JS, Martin JL, Azad AK, McCarthy TR, Kang PB, Voelker DR, Crouch EC, Schlesinger LS. Surfactant protein D increases fusion of Mycobacterium tuberculosis-containing phagosomes with lysosomes in human macrophages. Infect Immun 2006;74:7005-7009. (Pubitemid 44913176)
64. Kuroki Y, Takahashi M, Nishitani C. Pulmonary collectins in innate immunity of the lung. Cell Microbiol 2007;9:1871-1879. (Pubitemid 47087079)
65. Gaynor CD, McCormack FX, Voelker DR, McGowan SE, Schlesinger LS. Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages. J Immunol 1995;155:5343-5351.
66. Ferguson JS, Voelker DR, McCormack FX, Schlesinger LS. Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages. J Immunol 1999;163:312-321. (Pubitemid 29295855)
67. Daley CL, Small PM, Schecter GF, Schoolnik GK, McAdam RA, Jacobs WR Jr, Hopewell PC. 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;326:231-235.
68. + cytotoxic T cells and relative resistance of alveolar macrophages to lysis. J Immunol 1997;159:290-297.
69. + effector T cells in childhood tuberculosis. J Immunol 2007;179:1331-1339.
70. +Tcells recognizing CFP10 are recruited to the lung after Mycobacterium tuberculosis infection. J Exp Med 2004;200:1479-1489.
71. + T cells kill intracellular Mycobacterium tuberculosis by a perforin and Fas/Fas ligand-independent mechanism. J Immunol 2001;167:2734-2742.
72. + T cells preferentially recognize heavily infected cells. Am J Respir Crit Care Med 2003;168:1346-1352.
73. + T cells require perforin to kill target cells and provide protection in vivo. J Immunol 2008;181:8595-8603.
74. Jeyanathan M, Mu J, McCormick S, Damjanovic D, Small CL, Shaler C, Kugathasan K, Xing Z. Mechanisms of airway luminal antituberculosis memory. Am J Respir Crit Care Med 2010;181:862-872.
75. Dheda K, Chang JS, Lala S, Huggett JF, Zumla A, Rook GA. Gene expression of IL17 and IL23 in the lungs of patients with active tuberculosis. Thorax 2008;63:566-568. (Pubitemid 351831173)
76. Pasquinelli V, Townsend JC, Jurado JO, Alvarez IB, Quiroga MF, Barnes PF, Samten B, Garcia VE. IFN-γ production during active tuberculosis is regulated by mechanisms that involve IL-17, SLAM, and CREB. J Infect Dis 2009;199:661-665.
77. Cruz A, Khader SA, Torrado E, Fraga A, Pearl JE, Pedrosa J, Cooper AM, Castro AG. Cutting edge: IFN-γ regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. J Immunol 2006;177:1416-1420. (Pubitemid 44092473)
78. + T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 2007;8:369-377.
79. + T cells in regulation of the immune response during human tuberculosis. Clin Exp Immunol 2006;144:25-34.
80. Delgado JC, Tsai EY, Thim S, Baena A, Boussiotis VA, Reynes JM, Sath S, Grosjean P, Yunis EJ, Goldfeld AE. Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia. Proc Natl Acad Sci USA 2002;99:7576-7581. (Pubitemid 34568733)
81. Gong JH, Zhang M, Modlin RL, Linsley PS, Iyer D, Lin Y, Barnes PF. Interleukin-10 downregulates Mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression. Infect Immun 1996;64:913-918. (Pubitemid 26065567)
82. Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respir Crit Care Med 2006;173:803-810.
83. Hougardy JM, Place S, Hildebrand M, Drowart A, Debrie AS, Locht C, Mascart F. Regulatory T cells depress immune responses to protective antigens in active tuberculosis. Am J Respir Crit Care Med 2007;176:409-416. (Pubitemid 47267476)
84. + Treg cells inhibit human memory gammadelta T cells to produce IFN-γ in response to M. tuberculosis antigen ESAT-6. Blood 2008;111:5629-5636.
85. Boussiotis VA, Tsai EY, Yunis EJ, Thim S, Delgado JC, Dascher CC, Berezovskaya A, Rousset D, Reynes JM, Goldfeld AE. IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J Clin Invest 2000;105:1317-1325. (Pubitemid 30266085)
86. Joosten SA, van Meijgaarden KE, Savage ND, de Boer T, Triebel F, van der Wal A, de Heer E, Klein MR, Geluk A, Ottenhoff TH. Identification of a human CD81 regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci USA 2007;104:8029-8034. (Pubitemid 47185870)
87. Kursar M, Koch M, Mittrucker HW, Nouailles G, Bonhagen K, Kamradt T, Kaufmann SH. Cutting edge: regulatory T cells prevent efficient clearance of Mycobacterium tuberculosis. J Immunol 2007;178:2661-2665. (Pubitemid 46333142)
88. McGuirk P, Higgins SC, Mills KH. The role of regulatory T cells in respiratory infections and allergy and asthma. Curr Allergy Asthma Rep 2010;10:21-28.
89. Durrant DM, Metzger DW. Emerging roles of T helper subsets in the pathogenesis of asthma. Immunol Invest 2010;39:526-549.
90. Lane N, Robins RA, Corne J, Fairclough L. Regulation in chronic obstructive pulmonary disease: the role of regulatory T-cells and Th17 cells. Clin Sci (Lond) 2010;119:75-86.
91. + regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179:1121-1130.
92. Gerke AK, Hunninghake G. The immunology of sarcoidosis. Clin Chest Med 2008;29:379-390. (vii.).
93. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B. Transforming growth factor-β "reprograms" the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 2008;9:1341-1346.
94. Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, et al. TGF-β induces IL-9 production from human Th17 cells. J Immunol 2010;185:46-54.
95. + T cells and promotes allergic-induced airway inflammation independent of IL-4. J Immunol 2008;181:4780-4790.
96. Costello AM, Kumar A, Narayan V, Akbar MS, Ahmed S, Abou-Zeid C, Rook GA, Stanford J, Moreno C. Does antibody to mycobacterial antigens, including lipoarabinomannan, limit dissemination in childhood tuberculosis? Trans R Soc Trop Med Hyg 1992;86:686-692.
97. Glatman-Freedman A. Advances in antibody-mediated immunity against Mycobacterium tuberculosis: implications for a novel vaccine strategy. FEMS Immunol Med Microbiol 2003;39:9-16. (Pubitemid 37211454)
98. Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974;99:131-138.
99. Wallis RS, Pai M, Menzies D, Doherty TM, Walzl G, Perkins MD, Zumla A. Biomarkers and diagnostics for tuberculosis: progress, needs, and translation into practice. Lancet 2010;375:1920-1937.
100. Kagina BM, Abel B, Scriba TJ, Hughes EJ, Keyser A, Soares A, Gamieldien H, Sidibana M, Hatherill M, Gelderbloem S, et al.: South African Tuberculosis Vaccine Initiative. Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis, following BCG vaccination of newborns. Am J Respir Crit Care Med 2010;182:1073-1079.
101. Dheda K, Chang JS, Breen RA, Kim LU, Haddock JA, Huggett JF, Johnson MA, Rook GA, Zumla A. In vivo and in vitro studies of a novel cytokine, interleukin 4d2, in pulmonary tuberculosis. Am J Respir Crit Care Med 2005;172:501-508.
102. Rook GA, Dheda K, Zumla A. Immune responses to tuberculosis in developing countries: implications for new vaccines. Nat Rev Immunol 2005;5:661-667. (Pubitemid 41113197)
103. Barker LF, Brennan MJ, Rosenstein PK, Sadoff JC. Tuberculosis vaccine research: the impact of immunology. Curr Opin Immunol 2009;21:331-338.
104. Place S, Verscheure V, de San N, Hougardy JM, Schepers K, Dirix V, Dediste A, Michel O, Drowart A, Allard SD, et al. Heparin-binding, hemagglutinin-specific IFN-γ synthesis at the site of infection during active tuberculosis in humans. Am J Respir Crit Care Med 2010;182:848-854.
105. Dawson R, Condos R, Tse D, Huie ML, Ress S, Tseng CH, Brauns C, Weiden M, Hoshino Y, Bateman E, et al. Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis. PLoS ONE 2009;4:e6984.
106. Condos R, Raju B, Canova A, Zhao BY, Weiden M, Rom WN, Pine R. Recombinant γ interferon stimulates signal transduction and gene expression in alveolar macrophages in vitro and in tuberculosis patients. Infect Immun 2003;71:2058-2064. (Pubitemid 36368740)
107. Condos R, Hull FP, Schluger NW, Rom WN, Smaldone GC. Regional deposition of aerosolized interferon-γ in pulmonary tuberculosis. Chest 2004;125:2146-2155. (Pubitemid 38788183)
108. Dheda K, van Zyl SR, Badri M, Pai M. T-cell interferon-γ release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings. Curr Opin Pulm Med 2009; 15:188-200.
109. Dheda K, van Zyl-Smit RN, Sechi LA, Badri M, Meldau R, Meldau S, Symons G, Semple PL, Maredza A, Dawson R, et al. Utility of quantitative T-cell responses versus unstimulated interferon-γ for the diagnosis of pleural tuberculosis. Eur Respir J 2009;34:1118-1126.
110. Patel VB, Singh R, Connolly C, Coovadia Y, Peer AK, Parag P, Kasprowicz V, Zumla A, Ndung'u T, Dheda K. Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population. Am J Respir Crit Care Med 2010;182:569-577.
111. Dheda K, van Zyl-Smit RN, Meldau R, Meldau S, Symons G, Khalfey H, Govender N, Rosu V, Sechi LA, Maredza A, et al. Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis. Thorax 2009;64:847-853.
112. Kantrow SP, Meyer KC, Kidd P, Raghu G. The CD4/CD8 ratio in BAL fluid is highly variable in sarcoidosis. Eur Respir J 1997;10:2716-2721. (Pubitemid 28052776)
113. Horster R, Kirsten D, Gaede KI, Jafari C, Strassburg A, Greinert U, Kalsdorf B, Ernst M, Lange C. Antimycobacterial immune responses in patients with pulmonary sarcoidosis. Clin.Respir.J. 2009;3:229-238.
114. Cashmore TJ, Peter JG, van Zyl-Smit RN, Semple PL, Maredza A, Meldau R, Zumla A, Nurse B, Dheda K. Feasibility and diagnostic utility of antigen-specific interferon-γ responses for rapid immunodiagnosis of tuberculosis using induced sputum. PLoS ONE 2010;5:e10389.
115. Adetifa IM, Ota MO, Walther B, Hammond AS, Lugos MD, Jeffries DJ, Donkor SA, Adegbola RA, Hill PC. Decay kinetics of an interferon γ release assay with anti-tuberculosis therapy in newly diagnosed tuberculosis cases. PLoS ONE 2010;5:e12502.
116. Dheda K, Davids V, Lenders L, Roberts T, Meldau R, Ling D, Brunet L, van Zyl SR, Peter J, Green C, et al. Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS ONE 2010;5:e9848.
117. Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK, Natividad MP, Schmitt P, Wai J. Breath biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinb) 2010;90:145-151.