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Clinical and Translational Medicine
Published in: Clinical and Translational Medicine 1/2016

Open Access 01-12-2016 | Perspective

Adult pulmonary tuberculosis as a pathological manifestation of hyperactive antimycobacterial immune response

Author: Pawan Kumar

Published in: Clinical and Translational Medicine | Issue 1/2016

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Abstract

The intricate relationship between tuberculosis (TB) and immune system remains poorly understood. It is generally believed that weakening of the immune response against Mycobacterium tuberculosis leads to reactivation of latent infection into the active pulmonary disease. However, heterogeneous nature of TB and failure of rationally designed vaccines in clinical trials raises serious questions against the simplistic view of TB as an outcome of weakened immunity. In the wake of accumulating human TB data, it is argued here that a hyperactive antimycobacterial immune response is to blame for the pathogenesis of pulmonary TB in immunocompetent adults. Direct and indirect evidence supporting this notion is presented in this article. Revisiting the role of immune system in TB pathogenesis will pave the way for effective anti-TB vaccines.
Literature
1.
WHO. Global Tuberculosis Report 2014. World Health Organization; 2014
2.
3.
Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE et al (2005) TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med 11(6):653–660CrossRefPubMedPubMedCentral
4.
WHO: World Health Organization global tuberculosis control report 2009. Global tuberculosis control. 2011
5.
6.
7.
Behar S, Martin C, Booty M, Nishimura T, Zhao X, Gan H et al (2011) Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunol 4(3):279–287CrossRefPubMedPubMedCentral
8.
Chakravarty SD, Zhu G, Tsai MC, Mohan VP, Marino S, Kirschner DE et al (2008) Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. Infect Immun 76(3):916–926CrossRefPubMedPubMedCentral
9.
Harris J, Keane J (2010) How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin Exp Immunol 161(1):1–9PubMedPubMedCentral
10.
11.
Casanova J-L, Abel L (2002) Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol 20(1):581–620CrossRefPubMed
12.
Dorman SE, Picard C, Lammas D, Heyne K, van Dissel JT, Baretto R et al (2004) Clinical features of dominant and recessive interferon γ receptor 1 deficiencies. Lancet 364(9451):2113–2121CrossRefPubMed
13.
Alcaïs A, Quintana-Murci L, Thaler DS, Schurr E, Abel L, Casanova JL (2010) Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity? Ann NY Acad Sci 1214(1):18–33CrossRefPubMed
14.
Peters W, Ernst JD (2003) Mechanisms of cell recruitment in the immune response to Mycobacterium tuberculosis. Microb Infect 5(2):151–158CrossRef
15.
Egen JG, Rothfuchs AG, Feng CG, Winter N, Sher A, Germain RN (2008) Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas. Immunity 28(2):271–284CrossRefPubMedPubMedCentral
16.
Barnes PF (2001) Diagnosing latent tuberculosis infection: the 100-year upgrade. Am J Respir Crit Care Med 163(4):807–808CrossRefPubMed
17.
18.
Comstock GW, Livesay VT, Woolpert SF (1974) The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 99(2):131–138CrossRefPubMed
19.
Doherty TM, Demissie A, Olobo J, Wolday D, Britton S, Eguale T et al (2002) Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients. J Clin Microbiol 40(2):704–706CrossRefPubMedPubMedCentral
20.
Andersen P, Doherty TM, Pai M, Weldingh K (2007) The prognosis of latent tuberculosis: can disease be predicted? Trends Mol Med 13(5):175–182CrossRefPubMed
21.
Maher J, Kelly P, Hughes P, Clancy L (1992) Skin anergy and tuberculosis. Respir Med 86(6):481–484CrossRefPubMed
22.
Toossi Z, Ellner J (1996) Mechanisms of anergy in tuberculosis. Tuberculosis. Springer, Berlin, pp 221–238CrossRef
23.
Tsao T, Huang C, Chiou W, Yang P, Hsieh M, Tsao K (2002) Levels of interferon-γ and interleukin-2 receptor-α for bronchoalveolar lavage fluid and serum were correlated with clinical grade and treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis 6(8):720–727PubMed
24.
Verbon A, Juffermans N, Van Deventer S, Speelman P, Van Deutekom H, Van Der Poll T (1999) Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clin Exp Immunol 115(1):110CrossRefPubMedPubMedCentral
25.
Vordermeier HM, Chambers MA, Cockle PJ, Whelan AO, Simmons J, Hewinson RG (2002) Correlation of ESAT-6-specific gamma interferon production with pathology in cattle following Mycobacterium bovis BCG vaccination against experimental bovine tuberculosis. Infect Immun 70(6):3026–3032CrossRefPubMedPubMedCentral
26.
Berry MP, Graham CM, McNab FW, Xu Z, Bloch SA, Oni T et al (2010) An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466(7309):973–977CrossRefPubMedPubMedCentral
27.
Vynnycky E, Fine PE (2000) Lifetime risks, incubation period, and serial interval of tuberculosis. Am J Epidemiol 152(3):247–263CrossRefPubMed
28.
Verver S, Warren RM, Beyers N, Richardson M, van der Spuy GD, Borgdorff MW et al (2005) Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med 171(12):1430–1435CrossRefPubMed
29.
Wu-Hsieh BA, Chen C-K, Chang J-H, Lai S-Y, Wu CH, Cheng W-C et al (2001) Long-lived immune response to early secretory antigenic target 6 in individuals who had recovered from tuberculosis. Clin Infect Dis 33(8):1336–1340CrossRefPubMed
30.
Barber DL, Andrade BB, Sereti I, Sher A (2012) Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol 10(2):150–156PubMedPubMedCentral
31.
Murdoch DM, Venter WD, Van Rie A, Feldman C (2007) Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther 4(1):9CrossRefPubMedPubMedCentral
32.
Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC Jr et al (2005) Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. Aids 19(4):399–406CrossRefPubMed
33.
Mahnke YD, Greenwald JH, DerSimonian R, Roby G, Antonelli LR, Sher A et al (2012) Selective expansion of polyfunctional pathogen-specific CD4+ T cells in HIV-1 − infected patients with immune reconstitution inflammatory syndrome. Blood 119(13):3105–3112CrossRefPubMedPubMedCentral
34.
Bourgarit A, Carcelain G, Martinez V, Lascoux C, Delcey V, Gicquel B et al (2006) Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV co-infected patients. Aids 20(2):F1–F7CrossRefPubMed
35.
Sutherland JS, Young JM, Peterson KL, Sanneh B, Whittle HC, Rowland-Jones SL et al (2010) Polyfunctional CD4+ and CD8+ T cell responses to tuberculosis Antigens in HIV-1–infected patients before and after anti-retroviral treatment. J Immunol 184(11):6537–6544CrossRefPubMed
36.
Wilkinson KA, Seldon R, Meintjes G, Rangaka MX, Hanekom WA, Maartens G et al (2009) Dissection of regenerating T-Cell responses against tuberculosis in HIV-infected adults sensitized by Mycobacterium tuberculosis. Am J Respir Crit Care Med 180(7):674–683CrossRefPubMedPubMedCentral
37.
Bourgarit A, Carcelain G, Samri A, Parizot C, Lafaurie M, Abgrall S et al (2009) Tuberculosis-associated immune restoration syndrome in HIV-1-infected patients involves tuberculin-specific CD4 Th1 cells and KIR-negative γδ T cells. J Immunol 183(6):3915–3923CrossRefPubMed
38.
Meintjes G, Wilkinson KA, Rangaka MX, Skolimowska K, Van Veen K, Abrahams M et al (2008) Type 1 helper T cells and FoxP3-positive T cells in HIV–tuberculosis-associated immune reconstitution inflammatory syndrome. Am J Respir Crit Care Med 178(10):1083–1089CrossRefPubMedPubMedCentral
39.
Barber DL, Mayer-Barber KD, Antonelli LR, Wilson MS, White S, Caspar P et al (2010) Th1-driven immune reconstitution disease in Mycobacterium avium–infected mice. Blood 116(18):3485–3493CrossRefPubMedPubMedCentral
40.
41.
Sutaria N, Liu C-T, Chen TC (2014) Vitamin D status, receptor gene polymorphisms, and supplementation on tuberculosis: a systematic review of case-control studies and randomized controlled trials. J Clin Transl Endocrinol 1(4):151–160CrossRefPubMedPubMedCentral
42.
Nursyam EW, Amin Z, Rumende CM (2006) The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones 38(1):3–5PubMed
43.
44.
Cohen-Lahav M, Shany S, Tobvin D, Chaimovitz C, Douvdevani A (2006) Vitamin D decreases NFκB activity by increasing IκBα levels. Nephrol Dial Transplant 21(4):889–897CrossRefPubMed
45.
Chun RF, Adams JS, Hewison M (2011) Immunomodulation by vitamin D: implications for TB
46.
47.
Imazeki I, Matsuzaki J, Tsuji K, Nishimura T (2006) Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity. Biomed Res 27(1):1–9CrossRefPubMed
48.
Gorman S, Kuritzky LA, Judge MA, Dixon KM, McGlade JP, Mason RS et al (2007) Topically applied 1, 25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+ CD25+ cells in the draining lymph nodes. J Immunol 179(9):6273–6283CrossRefPubMed
49.
Smolders J, Menheere P, Thewissen M, Peelen E, Tervaert JWC, Hupperts R et al (2010) Regulatory T cell function correlates with serum 25-hydroxyvitamin D, but not with 1, 25-dihydroxyvitamin D, parathyroid hormone and calcium levels in patients with relapsing remitting multiple sclerosis. J Steroid Biochem Mol Biol 121(1):243–246CrossRefPubMed
50.
Herzmann C, Ernst M, Ehlers S, Stenger S, Maertzdorf J, Sotgiu G et al (2012) Increased frequencies of pulmonary regulatory T-cells in latent Mycobacterium tuberculosis infection. Eur Respir J 40(6):1450–1457CrossRefPubMed
51.
Herzmann C, Lange C, Stenger S, Maertzdorf J, Schaberg T, Sotgiu G et al (2012) Latent tuberculosis infection is associated with an increased frequency of Treg cells in the bronchoalveolar lavage. Pneumologie 66(11):P3_014
52.
Smego R, Ahmed N (2003) A systematic review of the adjunctive use of systemic corticosteroids for pulmonary tuberculosis. Int J Tuberc Lung Dis 7(3):208–213PubMed
53.
Kadhiravan T, Deepanjali S (2010) Role of corticosteroids in the treatment of tuberculosis. An evidence-based update
54.
Critchley JA, Young F, Orton L, Garner P (2013) Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 13(3):223–237CrossRefPubMed
55.
Vilaplana C, Marzo E, Tapia G, Diaz J, Garcia V, Cardona P-J (2013) Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J Infect Dis 208(2):199–202CrossRefPubMed
56.
Dutta NK, Mazumdar K, Dastidar SG, Park J-H (2007) Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice. Int J Antimicrob Agents 30(4):336–340CrossRefPubMed
57.
Ivanyi J, Zumla A (2013) Nonsteroidal antiinflammatory drugs for adjunctive tuberculosis treatment. J Infect Dis 208:153CrossRef
58.
Bansal K, Narayana Y, Patil SA, Balaji KNM (2009) bovis BCG induced expression of COX-2 involves nitric oxide-dependent and-independent signaling pathways. J Leukoc Biol 85(5):804–816CrossRefPubMed
59.
60.
Meintjes G, Skolimowska KH, Wilkinson KA, Matthews K, Tadokera R, Conesa-Botella A et al (2012) Corticosteroid-modulated immune activation in the tuberculosis immune reconstitution inflammatory syndrome. Am J Respir Crit Care Med 186(4):369–377CrossRefPubMedPubMedCentral
61.
Alcaïs A, Fieschi C, Abel L, Casanova J-L (2005) Tuberculosis in children and adults two distinct genetic diseases. J Exper Med 202(12):1617–1621CrossRef
62.
63.
Dubos RJ, Dubos J (1952) The white plague: tuberculosis, man, and society. Rutgers University Press, New Brunswick
64.
Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B (2008) Paediatric tuberculosis. Lancet Infect Dis 8(8):498–510CrossRefPubMed
65.
Young DB, Perkins MD, Duncan K, Barry CE III (2008) Confronting the scientific obstacles to global control of tuberculosis. J Clin Investig 118(4):1255CrossRefPubMedPubMedCentral
66.
Sharma S, Mohan A (2004) Extrapulmonary tuberculosis. Indian J Med Res 120(4):316PubMed
Metadata
Title
Adult pulmonary tuberculosis as a pathological manifestation of hyperactive antimycobacterial immune response
Author
Pawan Kumar
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Clinical and Translational Medicine / Issue 1/2016
Electronic ISSN: 2001-1326
DOI
https://doi.org/10.1186/s40169-016-0119-0

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