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Expert Review of Vaccines Volume 14, 2015 - Issue 12
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Reviews

Integrating knowledge of Mycobacterium tuberculosis pathogenesis for the design of better vaccines

Françoise MascartLaboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium;Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
&
Camille LochtUniv.Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000Lille, France;CNRS, UMR8204, F-59000Lille, France;Inserm, U1019, F-59000Lille, France;CHU Lille, F-59000, Lille, France;Institut Pasteur de Lille, F-59000, Lille, FranceCorrespondence[email protected]
Pages 1573-1585 | Published online: 30 Oct 2015

References

**Important meta-analysis that established the poor efficacy of BCG against adult pulmonary TB.

  • Kaufmann SHE, Lange C, Rao M, et al. Progress in tuberculosis vaccine development and host-directed therapies – a state of the art review. Lancet Respir Med. 2014;2:301–320.
  • Kaufmann SHE, Evans TG, Hanekom WA. Tuberculosis vaccines: time for a global strategy. Sci Transl Med. 2015;7:276sf8.
  • Tameris MD, Hatherill M, Landry BS, et al. MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013;381:1021–1028.

**The first efficacy data available for a viral-vectored TB vaccine destined to boost BCG-mediated protective immunity.

  • Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–969.
  • Kang BK, Azad AK, Torrelles JB, et al. The human macrophage mannose receptor directs Myobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J Exp Med. 2005;202:987–999.
  • Hu C, Mayadas-Norton T, Tanaka K, et al. Mycobacterium tuberculosis infection in complement receptor 3-deficient mice. J Immunol. 2000;165:2596–2602.
  • 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;144:2771–2780.
  • Weikert LF, Lopez JP, Abdolrasulnia R, et al. Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway. Am J Physiol Lung Cell Mol Physiol. 2000;279:L216–L223.
  • Nguyen L, Pieters J. The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages. Trends Cell Biol. 2005;15:269–276.
  • Chua J, Vergne I, Master S, et al. A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest. Curr Opin Microbiol. 2004;7:71–77.
  • Tan T, Lee WL, Alexander DC, et al. The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation. Cell Microbiol. 2006;8:1417–1429.
  • Walburger A, Koul A, Ferrari G, et al. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science. 2004;304:1800–1804.
  • McDonough KA, Kress Y, Bloom BR. Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages. Infect Immun. 1993;61:2763–2773.

*First report that M. tuberculosis can escape from the phagosome into the cytosol of infected macrophages.

  • Van Der Wel N, Hava D, Houben D, et al. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. 2007;129:1287–1298.
  • Simeone R, Bobard A, Lippmann J, et al. Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog. 2012;8:e1002507.
  • Guirado E, Schlesinger LS, Kaplan G. Macrophages in tuberculosis: friend or foe. Sem Immunol. 2013;35:563–583.
  • Ulrichs T, Kaufmann SH. New insights into the function of granulomas in human tuberculosis. J Pathol. 2006;208:261–269.
  • Voskuil MI, Schnappinger D, Harrell MI, et al. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med. 2003;198:705–713.
  • Rustad TR, Harrell MI, Liao R, et al. The enduring hypoxic response of Mycobacterium tuberculosis. PLoS One. 2008;3:e1502.
  • Ray JC, Flynn JL, Krischner DE. Synergy between individual TNF-dependent functions determines granuloma performance for controlling Mycobacterium tuberculosis infection. J Immunol. 2009;182:3706–3717.
  • Hernandez-Pando R, Jeyanathan M, Mengistu G, et al. Persistance of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet. 2000;356:2133–2138.

**Report on an important observation that M. tuberculosis can invade different cell types in the lungs during latent infection.

  • Neyrolles O, Hernandez-Pando R, Pietri-Rouxel F, et al. Is adipose tissue a place for Mycobacterium tuberculosis persistence? PLoS One. 2006;1:e43.
  • Chapeton-Montes JA, Plaza DF, Barrero CA, et al. Quantitative flow cytometric monitoring of invasion of epithelial cells by Mycobacterium tuberculosis. Front Biosci. 2008;13:650–656.
  • Mehta PK, King CH, White EH, et al. Comparison of in vitro models for the study of Mycobacterium tuberculosis invasion and intracellular replication. Infect Immun. 1996;64:2673–2679.
  • Ryndak MB, Singh KK, Peng Z, et al. Transcriptional profile of Mycobacterium tuberculosis replicating in type II alveolar epithelial cells. PLoS One. 2015;10:e0123745.
  • Bermudez LE, Sangari FJ, Kolonoski P, et al. The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infect Immun. 2002;70:140–146.
  • Delogu G, Sanguinetti M, Posteraro B, et al. The hbhA gene of Mycobacterium tuberculosis is specifically upregulated in the lungs but not in the spleens of aerogenically infected mice. Infect Immun. 2006;74:3006–3011.
  • Pethe K, Alonso S, Biet F, et al. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature. 2001;412:190–194.
  • Dobos KM, Spotts EA, Quinn FD, et al. Necrosis of lung epithelial cells during infection with Mycobacterium tuberculosis is preceded by cell permeation. Infect Immun. 2000;68:6300–6310.
  • Lin Y, Zhang M, Barnes PF. Chemokine production by a human alveolar epithelial cell line in response to Mycobacterium tuberculosis. Infect Immun. 1998;66:1121–1126.
  • Lowe DM, Redford PS, Wilkinson RJ, et al. Neutrophils in tuberculosis: friend or foe?. Trends Immunol. 2012;33:14–25.
  • Selwyn PA, Hartel D, Lewis VA, et al. A prospective study on the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med. 1989;320:545–550.
  • Barry CE 3rd, Boshoff HI, Dartois V, et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol. 2009;7:845–855.
  • Getahun H, Matteelli A, Chaisson RE, et al. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015;372:2127–2135.
  • Pai M, Denkinger CM, Kik SV, et al. Gamma interferon release assays for the detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014;27:3–20.

*Important review on the advantages and limitations of IFN-γ release assays for the diagnosis of latent M. tuberculosis infection.

  • Hougardy JM, Schepers K, Place S, et al. Heparin-binding-hemagglutinin-induced IFN-γ release as a diagnostic tool for latent tuberculosis. PLoS One. 2007;2:e926.
  • Govender L, Abel B, Hughes EJ, et al. Higher human CD4 T cell response to novel Mycobacterium tuberculosis latency associated antigens Rv2660 an Rv2659 in latent infection compared with tuberculosis cases. Vaccine. 2010;29:51–57.
  • Lin PL, Dietrich J, Tan E, et al. The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection. J Clin Invest. 2012;122:303–314.
  • Houghton J, Cortes T, Schubert O, et al. A small RNA encoded in the Rv2660c locus of Mycobacterium tuberculosis is induced during starvation and infection. PLoS One. 2013;8:e80047.
  • Wyndham-Thomas C, Dirix V, Shepers K, et al. Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube. BMC Infect Dis. 2015;15:59.
  • Smits K, Corbière V, Dirix V, et al. Immunological signatures identifying different stages of latent Mycobacterium tuberculosis infection and discriminating latent from active tuberculosis in humans. J Clin Cell Immunol. 2015;6:4.
  • Corbière V, Pottier G, Bonkain F, et al. Risk stratification of latent tuberculosis defined by combined interferon gamma release assays. PLoS One. 2012;7:e43285.
  • Schnappinger D, Ehrt S, Voskuil MI, et al. Transcriptional adaptation of Mycobacterium tuberculosis with macrophages: insights into the phagosomal environment. J Exp Med. 2003;198:693–704.
  • Karakousis PC, Yoshimatsu T, Lamichhane G, et al. Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice. J Exp Med. 2004;200:647–657.
  • Cappelli G, Volpe E, Grassi M, et al. Profiling of Mycobacterium tuberculosis gene expression during human macrophage infection: upregulation of the alternative sigma factor G, a group of transcriptional regulators, and proteins with unknown functions. Res Microbiol. 2006;157:445–455.
  • Leyten EM, Lin MY, Franken KL, et al. Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis. Microbes Infect. 2006;8:2052–2060.
  • Demissie A, Leyten EM, Abebe M, et al. Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infection with Mycobacterium tuberculosis. Clin Vaccine Immunol. 2006;13:179–186.
  • Schuck SD, Mueller H, Kunitz F, et al. Identification of T-cell antigens specific for latent Mycobacterium tuberculosis infection. PLoS One. 2009;4:e5590.
  • Commandeur S, Van Meijgaarden KE, Prins C, et al. An unbiased genome-wide Mycobacterium tuberculosis gene expression approach to discover antigens targeted by human T cells expressed during pulmonary infection. J Immunol. 2013;190:1659–1671.
  • Serra-Vidal MM, Latorre I, Franken KL, et al. Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis. Front Microbiol. 2014;5:517.
  • Goletti D, Butera O, Vanni V, et al. Response to Rv2628 latency antigen associates with cured tuberculosis and remote infection. Eur Respir J. 2010;36:135–142.
  • Delogu G, Chiacchio T, Vanini V, et al. Methylated HBHA produced in M. smegmatis discriminates between active and non-active tuberculosis disease. PLoS One. 2011;6:e18315.
  • Loxton AG, Black GF, Stanley K, et al. Heparin-binding hemagglutinin induces IFN-γ+IL-2+IL-17+ multifunctional CD4+ T cells during latent but not active tuberculosis disease. Clin Vaccine Immunol. 2012;19:746–751.
  • Verwaerde C, Debrie AS, Dombu C, et al. HBHA vaccination may require both Th1 and Th17 immune responses to protect mice against tuberculosis. Vaccine. 2014;32:6240–6250.
  • Hutchinson P, Barkham TM, Tang W, et al. Measurement of phenotype and absolute number of circulating heparin-binding hemagglutinin, ESAT-6 and CFP10, and purified protein derivative antigen-specific CD4 T cells can discriminate active from latent tuberculosis. Clin Vaccine Immunol. 2015;22:200–212.
  • Sutherland JS, Im A, Pc H, et al. Pattern and diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease. Eur J Immunol. 2009;39:723–729.
  • Caccamo N, Guggino G, Joosten SA, et al. Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection. Eur J Immunol. 2010;40:2211–2220.
  • Qiu Z, Zhang M, Zhu Y, et al. Multifunctional CD4 T cell responses in patients with active tuberculosis. Sci Rep. 2012;2:216.
  • Chegou NN, Essone PN, Loxton AG, et al. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS One. 2012;7:e38501.
  • Frahm M, Goswami ND, Owzar K, et al. Discriminating between latent and active tuberculosis with multiple biomarker responses. Tuberculosis. 2011;91:250–256.
  • Tebruegge M, Dutta B, Donath S, et al. Mycobacteria-specific cytokine responses detect tuberculosis infection and distinguish latent from active tuberculosis. Am J Respir Crit Care Med. 2015;192:485–499.
  • Harrari A, Rozot V, Bellutti Enders F, et al. Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med. 2011;17:372–376.
  • Sutherland JS, De Jong BC, Jeffries DJ, et al. Production of TNF-α, IL-12(p40) and IL-17 can discriminate between active TB disease and latent infection in a West Africa cohort. PLoS One. 2010;5:e12365.
  • 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;119:1167–1177.
  • Bastian M, Braun T, Bruns H, et al. Mycobacterial lipopeptides elicit CD4+ CTLs in Mycobacterium tuberculosis-infected humans. J Immunol. 2008;180:3436–3446.
  • Lenzini L, Rottoli P, Rottoli L. The spectrum of human tuberculosis. Clin Exp Immunol. 1977;27:230–237.
  • Dwyer JM, Kantor FS. Regulation of delayed hypersensitivity. Failure to transfer delayed hypersensitivity to desensitize guinea pigs. J Exp Med. 1973;137:32–41.
  • Watson SR, Collins FM. Development of suppressor T cells in mice heavily infected with mycobacteria. Immunology. 1980;39:367–373.
  • Ellner JJ. Suppressor adherent cells in human tuberculosis. J Immunol. 1978;121:2573–2579.
  • Turcotte R, Lemieux S. Mechanisms of action of BCG-induced suppressor cells in mitogen-induced blastogenesis. Infect Immun. 1982;36:263–270.
  • Boussiotis VA, Tsai EY, Yunis EJ, et al. IL-10-producing T cell suppress immune responses in anergic tuberculosis patients. J Clin Invest. 2000;105:1317–1325.
  • Turner J, Gonzalez-Juarrero M, Ellis DL, et al. In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J Immunol. 2002;169:6343–6351.
  • Bonecini-Almeida MG, Ho JL, Boechat N, et al. Down-modulation of lung immune responses by interleukin-10 and transforming growth factor beta (TGF-beta) and analysis of TGF-beta receptors I and II in active tuberculosis. Infect Immun. 2004;72:2628–2634.
  • 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;180:2069–2073.
  • Ribeiro-Rodrigues C, Co T R, Rojas R, et al. A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis. Clin Exp Immunol. 2006;144:25–34.

*First report on the potential role of CD4+CD25+ T cells in human tuberculosis.

  • Hougardy JM, Place S, Hildebrand M, et al. Regulary T cells depress immune responses to protective antigens in active tuberculosis. Am J Respir Crit Care Med. 2007;176:409–416.
  • Hougardy JM, Verscheure V, Locht C, et al. In vitro expansion of CD4+CD25highFOXP3+CD127low/- regulatory T cells from peripheral blood lymphocytes of healthy M. tuberculosis-infected humans. Microbes Infect. 2007;9:1325–1332.
  • 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;204:2159–2169.
  • Semple PL, Binder AB, Davids M, et al. Regulatory T cells attenuate mycobacterial stasis in alveolar and blood-derived macrophages from patients with tuberculosis. Am J Respir Crit Care Med. 2013;187:1249–1258.
  • Schepers K, Dirix V, Mouchet F, et al. Early cellular immune response to a new candidate mycobacterial vaccine antigen in childhood tuberculosis. Vaccine. 2015;33:1077–1083.
  • Vanden Eijnden S, Goriely S, De Wit D, et al. Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns. Eur J Immunol. 2006;36:21–26.
  • Khader SA, Pearl JE, Sakamoto K, et al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-γ responses if IL-12p70 is available. J Immunol. 2005;175:788–795.
  • Roy A, Eisenhut M, Harris RJ, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systemic review and meta-analysis. Brit Med J. 2014;349:g4643.
  • Netea MG, Van Crevel R. BCG-induced protection: effects on innate immune memory. Semin Immunol. 2014;26:512–517.
  • Glatman-Freedman A, Casadevall A. Serum therapy for tuberculosis revisited: reappraisal of the role of antibody-mediated immunity against Mycobacterium tuberculosis. Clin Microbiol Rev. 1998;11:514–532.

*Important comprehensive review on the potential role of antibodies in protection against M. tuberculosis infection and TB disease.

  • Teitelbaum R, Glatman-Freedman A, Chen B, et al. A mAb recognizing a surface ant0igen of Mycobacterium tuberculosis enhances host survival. Proc Natl Acad Sci USA. 1998;95:15688–15693.
  • Achkar JM, Chan J, Casadevall A. B cells and antibodies in the defense against Mycobacterium tuberculosis infection. Immunol Rev. 2015;264:167–181.
  • Balu S, Relhic R, Lewis MJ, et al. A novel human IgA monoclonal antibody protects against tuberculosis. J Immunol. 2011;186:3113–3119.
  • Ernst JD. The immunological life cycle of tuberculosis. Nat Rev Immunol. 2012;12:581–591.
  • Khader SA, Cooper AM. IL-23 and IL-17 in tuberculosis. Cytokine. 2008;41:79–83.
  • Fedatto PF, Sergio CA, Paula MA, et al. Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4+/CD4+Foxp3+ cells. Immunology. 2012;137:239–248.
  • Bhattcharya D, Dwivedi VP, Kumar S, et al. Simultaneous inhibition of T helper 2 and T regulatory Cell differentiation by small molecules enhances bacillus Calmette-Guérin vaccine efficacy against tuberculosis. J Biol Chem. 2014;289:33404–33411.
  • Shafiani S, Tucker-Heard G, Kariyoe A, et al. Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis. J Exp Med. 2010;207:1409–1420.
  • Temmerman S, Pethe K, Parra M, et al. Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin. Nat Med. 2004;10:935–941.
  • Rouanet C, Debrie AS, Lecher S, et al. Subcutaneous boosting with heparin-binding haemagglutinin increases BCG-induced protection against tuberculosis. Microbes Infect. 2009;11:995–1001.
  • Aagaard C, Hoang T, Dietrich J, et al. A multistage tuberculosis vaccine that confers protection before and after exposure. Nat Med. 2011;17:189–194.
  • Reece ST, Nasser-Eddine A, Dietrich J, et al. Improved long-term protection against Mycobacterium tuberculosis Beijing/W in mice after intra-dermal inoculation of recombinant BCG expressing latency associated antigens. Vaccine. 2011;47:8740–8744.
  • WHO. The treatment of tuberculosis: guidelines. 4th ed. Document WHO/HTM/TB/2009.420. Geneva: World Health Organization;2010.
  • Gengiah TN, Gray AL, Naidoo K, et al. Initiating antiretrovirals during tuberculosis treatment: a drug safety review. Exp Opin Drug Saf. 2011;10:559–574.
  • Zumla A, Chakaya J, Centis R, et al. Tuberculosis treatment and management – an update on treatment regimens, trials new drugs, and adjunct therapies. Lancet Respir Med. 2015;3:220–234.
  • Gröschel MI, Prabowo SA, Cardona PJ, et al. Therapeutic vaccines for tuberculosis – a systematic review. Vaccine. 2014;32:3162–3168.
  • Lowrie DB, Tascon RE, Bonato VL, et al. Therapy of tuberculosis in mice with DNA vaccination. Nature. 1999;400:269–271.
  • Turner OC, Roberts AD, Frank AA, et al. Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis. Infect Immun. 2000;68:3674–3679.
  • Yu DH, Hu XD, Cai H. Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83. Gene Ther. 2008;15:652–659.
  • Changhong S, Hai Z, Limei W, et al. Therapeutic efficacy of a tuberculosis DNA vaccine encoding heat shock protein 65 of Mycobacterium tuberculosis and the human interleukin 2 fusion gene. Tuberculosis. 2009;89:54–61.

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