Immunological aspects of tuberculosis pathogenesis


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Abstract

The morphological aspects of TB pathogenesis are well described in the publications. Much is also known about the main stages of development and formation of specific adaptive immunity. However, from our point of view, not enough attention is being paid to the involvement of the immune system in the pathogenesis of clinically relevant TB abnormalities, as well as various forms of the disease. Nevertheless, there is no doubt that the variety of clinical manifestations of any disease associated with the penetration of a foreign agent into the body, and Mycobacterium tuberculosis (MTB) in particular, is due to the collective interaction of the infectious agent and the individual response of the macroorganism to this infectious agent. The mosaic of such interactions usually imposes its own adjustments on the development of different forms of the process, its speed and direction, as well as the outcomes. Certainly, the response of a macroorganism to MTB is an integral part of pathogenesis and consists of many general components including the responses associated with the mechanisms of natural and acquired immunity. Intensity of these reactions depends on the characteristics of an agent (MTB) and a macroorganism. For the development of TB disease, massiveness of TB infection, dose and duration of MTB exposure to the human body, as well as virulence of MTB and the level of body's protection during the exposure play a very important role. TB pathogenesis is somewhat different in primary MTB infection and re - infection. With primary infection, 88-90% of individuals do not have clinical manifestations, and only the tuberculin skin test conversion signals the onset of infection. In some cases, without any use of anti-TB drugs limited abnormalities may result in spontaneous cure with the minimal residual changes in the lungs, intrathoracic lymph nodes and tissues of other organs, often in the form of calcifications and limited areas of fibrosis in more advanced cases. Only 10-12% of newly infected individuals develop TB with severe clinical manifestations requiring TB therapy. The absence of clinical manifestations of primary TB infection can be explained by a high level of natural resistance of the human body to tuberculosis, and sometimes can be an effect of acquired protection due to BCG vaccination. This review attempts to discuss the role of immune mechanisms in the pathogenesis both at the beginning of disease development, and in the process of its various manifestations. Issues of genetically determined resistance or susceptibility to TB are not being covered in detail in this manuscript.

About the authors

V Ja Gergert

Central TB Research Institute Department of Immunology

Email: hergertv@mail.ru
проф., зав. отд. иммунологии ФГБНУ «ЦНИИТ» Moscow, Russia

M M Averbakh

Central TB Research Institute Department of Immunology

проф., г.н.с. отд. иммунологии ФГБНУ «ЦНИИТ» Moscow, Russia

A E Ergeshov

Central TB Research Institute Department of Immunology

проф., директор ФГБНУ «ЦНИИТ» Moscow, Russia

References

  1. Jahnsen F.L, Strickland D.H, Thomas J.A, Tobagus I.T, Napoli S, Zosky G.R, Turner D.J, Sly P.D, Stumbles P.A, Holt P.G. Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus. J Immunol. 2006;177:5861-7. doi: 10.4049/jimmunol.177.9.5861
  2. Agace W.W. Tissue - tropic effector T cells: generation and targeting opportunities. Nature Rev Immunol. 2006;6:682-92. doi: 10.1038/nri1869
  3. Lund F.E, Hollifield M, Schuer K, Lines J.L, Randall T.D, Garvy B.A. B cells are required for generation of protective effector and memory CD4 cells in response to pneumocystis lung infection. J Immunol. 2006;176: 6147-54. doi: 10.4049/jimmunol.176.10.6147
  4. Holt P.G, Sedgwick J.D. Suppression of IgE responses following antigen inhalation: a natural homeostatic mechanism, which limits sensitization to aeroallergens. Immunol Today. 1987;8:14-5. doi: 10.1016/0167-5699(87)90825-5
  5. Ерохин В.В. Функциональная морфология легких. М.: Медицина, 1987.
  6. Contoli M, Message S.D, Laza-Stanca V, Edwards M.R, Wark P.A, Bartlett N.W, Kebadze T, Mallia P, Stanciu L.A, Parker H.L, Slater L, Lewis-Antes A, Kon O.M, Holgate S.T, Davies D.E, Kotenko S.V, Papi A, Johnston S.L. Role of deficient type III interferon - γ production in asthma exacerbations. Nature Med. 2006;12: 1023-6. doi: 10.1038/nm1462
  7. Cox G, Gauldie J, Jordana M. Bronchial epithelial cell - derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils in vitro. Am J Respir Cell Mol Biol.1992;7:507-13. doi: 10.1165/ajrcmb/7.5.507
  8. Kato A, Truong-Tran A.Q, Scott A.L, Matsumoto K, Schleime R.P. Airway epithelial cells produce B cell - activating factor of TNF family by an IFN-beta - dependent mechanism. J Immunol. 2006;177:7164-72. doi: 10.4049/jimmunol.177.10.7164
  9. Eruslanov E.B, Lyadova.IV, Kondratieva T.K, Majorov K.B, Scheglov I.V, Orlova M.O, Apt A.S. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect Immun. 2005 Mar;73(3):1744-53. doi: 10.1128/IAI.73.3.1744-1753.2005
  10. González-Cortés C, Reyes-Ruvalcaba D, Diez-Tascón C, Rivero-Lezcano O.M. Apoptosis and oxidative burst in neutrophils infected with Mycobacterium spp. Immunol Lett. 2009 Sep 22;126(1-2):16-21. doi: 10.1016/j.imlet.2009.07.006
  11. Martineau A.R, Newton S.M, Wilkinson K.A, Kampmann B, Hall B.M, Nawroly N, Packe G.E, Davidson R.N, Griffiths C.J, Wilkinson R.J. Neutrophil - mediated innate immune resistance to mycobacteria. J Clin Invest. 2007 Jul;117(7):1988-94. doi: 10.1172/JCI31097
  12. Easton D.M, Nijnik A, Mayer M.L, Hancock R.E.W. Potential of immunomodulatory host defense peptides as novel anti - infectives. Trends in Biotechnology. 2009;27(10):582-90. doi: 10.1016/j.tibtech.2009.07.004
  13. Еремеев В.В., Гергерт В.Я. Изучение способности препарата глутоксим влиять на антибактериальную активность фагоцитов чуствительных и устойчивых к туберкулезу мышей. Туберкулез и болезни легких. 2013;7:43-7.
  14. Szereday L, Baliko Z, Szekeres-Bartho J. T-cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy. Clin Exp Immunol. 2003;131:287-91. doi: 10.1046/j.1365-2249.2003.02063.x
  15. Huang D, Shen Y, Qiu L, et al. Immune distribution and localization of phosphoantigen - specific Vγ2Vδ2 T cells in lymphoid and nonlymphoid tissues in Mycobacterium tuberculosis infection. Infect Immunol. 2008;76:426-36. doi: 10.1128/IAI.01008-07
  16. Cole S.T, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. Erratum in: Nature. 1998 Nov 12;396(6707):190.
  17. Апт А.С., Кондратьева Т.К. Туберкулез: патогенез, иммунный ответ и генетика хозяина. Молекулярная биология. 2008;42(5):880-90.
  18. Di Pietrantonio T, Correa.JA, Orlova M, Behr M.A, Schurr E. Joint effects of host genetic background and mycobacterial pathogen on susceptibility to infection. Infect Immun. 2011 Jun;79(6):2372-8. doi: 10.1128/IAI.00985-10
  19. Galli S.J, Kalesnikoff J, Grimbaldeston M.A, Piliponsky A.M, Williams C.M, Tsai M. Mast Cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749-86. doi: 10.1146/annurev.immunol.21.120601.141025
  20. Tupin E, Kinjo Y, Kronenberg, M. The unique role of natural killer T cells in the response to microorganisms. Nature Rev Microbiol. 2007;5:405-17. doi: 10.1038/nrmicro1657
  21. Cooper A.M, Khader S.A. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev. 2008;226:191-204. doi: 10.1111/j.1600-065X.2008.00702.x
  22. Orme I.M, Basaraba R.J. The formation of the granuloma in tuberculosis infection. Seminars in Immunology. 2014;26:601-9. doi: 10.1016/j.smim.2014.09.009
  23. Van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J, Brenner M, Peters P.J. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. 2007 Jun 29;129(7):1287-98. doi: 10.1016/j.cell.2007.05.059
  24. Schaible U.E, Winau F, Sieling P.A, Fischer K, Collins H.L, Hagens K, Modlin R.L, Brinkmann V, Kaufmann S.H. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med. 2003;9(8):1039-46. doi: 10.1038/nm906
  25. Winau F, Weber S, Sad S, de Diego J, Hoops S.L, Breiden B, Brinkmann V, Kaufmann S.H, Schaible U.E. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity. 2006 Jan; 24(1):105-17. doi: 10.1016/j.immuni.2005.12.001
  26. Deretic V. Autophagy, an immunologic magic bullet: Mycobacterium tuberculosis phagosome maturation block and how to bypass it. Future Microbiol. 2008 Oct;3(5):517-24. doi: 10.2217/17460913.3.5.517
  27. Prezzemolo T, Guggino G, La Manna M.P, Di Liberto D, Dieli F, Caccamo N. Functional Signatures of Human CD4 and CD8 T Cell Responses to Mycobacterium tuberculosis. Front Immunol. 2014;5:180. doi: 10.3389/fimmu.2014.00180
  28. Belkaid Y, Tarbell K. Regulatory T cells in the control of host - microorganism interactions. Annu Rev Immunol. 2009;27:551-89. doi: 10.1146/annurev.immunol.021908.132723
  29. Guyot-Revol V, Innes J.A, Hackforth S, Hinks T, Lalvani A. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respiratory and Critical Care Medicine. 2006;173(7):803-10. doi: 10.1164/rccm.200508-1294OC
  30. Ottenhoff T.H, Kaufmann S.H. Vaccines against tuberculosis: where are we and where do we need to go. PLoS Pathog. 2012;8(5):e1002607. doi: 10.1371/journal.ppat.1002607
  31. Stenger S, Hanson D.A, Teitelbaum R, Dewan P, Niazi K.R, Froelich C.J, Ganz T, Thoma-Uszynski S, Melián A, Bogdan C, Porcelli S.A, Bloom B.R, Krensky A.M, Modlin R.L. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science. 1998 Oct 2;282(5386):121-5. doi: 10.1126/science.282.5386.121
  32. Ulrichs T, Kaufmann S.H.E. New insights into the function of granulomas in human tuberculosis. J Pathol. 2006 Jan;208(2):261-9. doi: 10.1002/path.1906
  33. Cardona P.J, Llatjos R, Gordillo S, Díaz J, Ojanguren I, Ariza A, Ausina V. Evolution of granulomas in lungs of mice infected aerogenially with Mycobacterium tuberculosis. Scand J Immunol. 2000;52:156-63. doi: 10.1046/j.1365-3083.2000.00763.x
  34. Peyron P, Vaubourgeix J, Poquet Y, et al. Foamy Macrophages from Tuberculous Patients’Granulomas Constitute a Nutrient-Rich Reservoir for M.tuberculosis Persistence. PLoS Pathog. 2008;4:1-14. doi: 10.1371/journal.ppat.1000204
  35. Ulfichs T, Kosmiadi G.A, Trusov V, Jörg S, Pradl L, Titukhina M, Mishenko V, Gushina N, Kaufmann S.H. Human tuberculosis granulomas induce peripheral lymphoid follicle - like structures to orchestrate local host defence in the lung. J Pathol. 2004;204:217-28. doi: 10.1002/path.1628
  36. Mustafa T, Wiker H.G, Mørkve O, Sviland L. Differential expression of mycobacterial antigen MPT64, apoptosis and inflammatory markers in multinucleated giant cells and epithelioid cells in granulomas caused by Mycobacterium tuberculosis. Virchows Arch. 2008;452:449-56. doi: 10.1007/s00428-008-0575-z
  37. Ерохин В.В. Морфофункциональное состояние клеток легких при туберкулезном воспалении. В кн.: Клеточная биология легких в норме и при патологии. М.: Медицина, 2000:422-448.
  38. Dannenberg A.M. Jr. Roles of cytotoxicdelayed - typehypersensitivity and macrophage - activating cell - mediated immunity in the pathogenesis of tuberculosis. Immunobiology. 1994;191(4-5):461-73. doi: 10.1016/S0171-2985(11)80452-3
  39. Hunter R.L. Pathology of post primary tuberculosis of the lung: an illustrated critical review. Tuberculosis (Edinb). 2011;91(6):497-509. doi: 10.1016/j.tube.2011.03.007
  40. Hunter R.L, Jagannath C, Actor J.K. Pathology of postprimary tuberculosis in humans аnd mice:contradiction of long - held beliefs. Tuberculosis (Edinb). 2007;87(4):267-78. doi: 10.1016/j.tube.2006.11.003
  41. Hunter R.L, Olsen M, Jagannath C, Actor J.K. Trehalose-6, 6.-dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice. Am J Pathol. 2006;168(4):1249-61. doi: 10.2353/ajpath.2006.050848
  42. Rhoades E.R, Geisel R.E, Butcher B.A, Mc Donough S, Russell D.G. Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components. Tuberculosis (Edinb). 2005;85(3):159-76. doi: 10.1016/j.tube.2004.10.001
  43. Dannenberg A.M. Jr. Liquefaction and cavity formation in pulmonary TB: asimple method in rabbit skin to test inhibitors. Tuberculosis (Edinb). 2009;89(4):243-7. doi: 10.1016/j.tube.2009.05.006
  44. Volkman H.E, Pozos T.C, Zheng J, Davis J.M, Rawls J.F, Ramakrishnan L. Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science. 2010;327(5964):466-9. doi: 10.1126/science.1179663
  45. Elkington P, Shiomi T, Breen R, Nuttall R.K, Ugarte-Gil C.A, Walker N.F, Saraiva L, Pedersen B, Mauri F, Lipman M, Edwards D.R, Robertson B.D, D'Armiento J, Friedland J.S. MMP-1 drives immunopathology in human tuberculosis and transgenic mice. J Clin Invest. 2011;121(5):1827-33. doi: 10.1172/JCI45666
  46. Mehra S, Pahar B, Dutta N.K, Conerly C.N, Philippi-Falkenstein K, Alvarez X, Kaushal D. Transcriptional reprogramming in nonhuman primate (rhesus macaque) tuberculosis granulomas. PLoS One. 2010;5(8):e12266. doi: 10.1371/journal.pone.0012266
  47. Walker N.F, Clark S.O, Oni T, Andreu N, Tezera L, Singh S, Saraiva L, Pedersen B, Kelly D.L, Tree J.A, D'Armiento J.M, Meintjes G, Mauri F.A, Williams A, Wilkinson R.J, Friedland J.S, Elkington P.T. Doxycycline and HIV infection suppress tuberculosis - induced matrix metalloproteinases. Am J Respir Crit Care Med. 2012; 185(9):989-97. doi: 10.1164/rccm.201110-1769OC
  48. Kubler A, Luna B, Larsson C, Ammerman N.C, Andrade B.B Orandle M, Bock K.W, Xu Z, Bagci U, Mollura D.J, Marshall J, Burns J, Winglee K, Ahidjo B.A, Cheung L.S, Klunk M, Jain S.K, Kumar N.P, Babu S, Sher A, Friedland J.S, Elkington P.T, Bishai W.R. Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterialproliferation. J Pathol. 2015;235(3):431-44. doi: 10.1002/path.4432
  49. Horwitz M.A, Harth G. A new vaccine against tuberculosis affords greater survival after challenge than the current vaccinein the guinea pig model of pulmonary tuberculosis. Infect Immun. 2003;71(4):1672-9. doi: 10.1128/iai.71.4.1672-1679.2003
  50. Calderon V.E, Valbuena G, Goez Y, Judy B.M, Huante M.B, Sutjita P, Johnston R.K, Estes D.M, Hunter R.L, Actor J.K, Cirillo J.D, Endsley J.J. A humanized mouse model of tuberculosis. PLoS One. 2013;8(5):e 63331. doi: 10.1371/journal.pone.0063331
  51. Barry S, Breen R, Lipman M, Johnson M, Janossy G. Impaired antigen - specific CD4(+) T-lymphocyte responses in cavitary tuberculosis. Tuberculosis (Edinb). 2009;89(1):48-53. doi: 10.1016/j.tube.2008.07.002
  52. Hager M, Cowland J.B, Borregaard N. Neutrophil granules in health and disease. J Intern Med. 2010;268(1):25-34. doi: 10.1111/j.1365-2796.2010.02237.x
  53. Ong C.W, Elkington P.T, Brilha S, Ugarte-Gil C, Tome-Esteban M.T, Tezera L.B, Pabisiak P.J, Moores R.C, Sathyamoorthy T, Patel V, Gilman R.H, Porter J.C, Friedland J.S. Neutrophil - derived MMP-8 drives AMPK-dependent matrix destruction in human pulmonary tuberculosis. PLoS Pathog. 2015;11(5):e1004917. doi: 10.1371/journal.ppat.1004917
  54. Orme I.M. A new unifying theory of the pathogenesis of tuberculosis. Tuberculosis (Edinb). 2014; 94(1):8-14. doi: 10.1016/j.tube.2013.07.004
  55. Guidry T.V, Hunter R.L.Jr, Actor J.K. Mycobacterial glycolipid trehalose 6,6’-dimycolate - induced hypersensitive granulomas: contribution of CD4+ lymphocytes. Microbiology. 2007;153(Pt10):3360-9. doi: 10.1099/mic.0.2007/010850-0
  56. Dorhoi A, Reece S.T, Kaufmann S.H.E. Immunity to intracellular bacteria. In: Paul W.E (ed) Fundamental Immunology, 7th edn. Wolters Kluwer Health, Lippincott Williams & Wilkins, Philadelphia. 2012:973-1000. doi: 10.1002/eji.201141548
  57. Kaplan G, Post F.A, Moreira A.L, Wainwright H, Kreiswirth B.N Tanverdi M, Mathema B, Ramaswamy S.V, Walther G, Steyn L.M, Barry C.E 3rd, Bekker L.G. Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity. Infect Immun. 2003;71(12):7099-108. doi: 10.1128/iai.71.12.7099-7108.2003
  58. Welsh K.J, Risin S.A, Actor J.K, Hunter R.L. Immunopathology of postprimary tuberculosis: increased T regulatory cells and DEC-205-positive foamy macrophages in cavitary lesions. Clin Dev Immunol. 2011:307631. doi: 10.1155/2011/307631
  59. Subbian S, Tsenova L, Yang G, O’Brien P, Parsons S, Peixoto B, Taylor L, Fallows D, Kaplan G. Chronic pulmonary cavitary tuberculosis in rabbits: a failed host immune response. Open Biol1. 2011;(4):110016. doi: 10.1098/rsob.110016
  60. Nedeltchev G.G, Raghunand T.R, Jassal M.S, Lun S, Cheng Q.J, Bishai W.R. Extrapulmonary dissemination of Mycobacterium bovis but not Mycobacterium tuberculosis in a bronchoscopic rabbit model of cavitary tuberculosis. Infect Immun. 2009;77(2):598-603. doi: 10.1128/IAI.01132-08
  61. Gideon H.P, Phuah J, Myers A.J, et al. Variability in tuberculosis granuloma T cell responses exists, but a balance of pro - and anti - inflammatory cytokines is associated with sterilization. PLoS Pathog. 2015;11(1): e1004603.
  62. Гергерт В.Я, Авербах М.М., Космиади Г.А, Абрамова З.П., Хоменко И.С. Цитокины при туберкулезе (обзор). Вестник РАМН. 1995;7:33-8

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