Skip to main content
SpringerLink
Log in

The Inflammatory Response in Mycobacterium Tuberculosis Infection

  • Chapter
Book cover Inflammation

Abstract

Infection with Mycobacterium tuberculosis (MTB) is accompanied by an intense local inflammatory response which may be critical to the pathogenesis of tuberculosis. Activation of components of the innate immune response, such as recruitment of polymorphonuclear (PMN) and mononuclear phagocytes and induction of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), by MTB occurs early after MTB infection, however, may persist as the organism establishes itself within granulomas. MTB and its protein and non-protein components are potent in induction of cytokines and chemokines from PMN and monocytes. This review focuses on the interaction of MTB and the host with regard to activation of the innate immune response. It also attempts to identify the potential impact of this early response on the subsequent pathogenesis of MTB, and its role in development and extent of tuberculosis. Insights into the initiation and persistent of the inflammatory response may allow the application of anti-inflammatory agents as adjuncts in the treatment of tuberculosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abou-Zeid C., Ratliff T. L., Wiker H. G., Harboe M., Bennedsen J. and Rock G. A. W. (1988): Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovin BCG. Infect. Immun., 56, 3046–3047.

    PubMed  CAS  Google Scholar 

  • Actor J. K., Olsen M., Jagannath C. and Hunter R. L. (1999): Relationship of survival, organism containment, and acute murine tuberculosis. J. Interferon Cytokine Res., 19, 1183–1193.

    Article  PubMed  CAS  Google Scholar 

  • Aung H., Toossi Z., Wisnieski J. J., Culp L. A., Phillips N. B., Averill L. E., Daniel T. M. and Ellner J. J. (1996): Induction expression of tumor necrosis factor alpha by the 30 kDa alpha anti- gen of Mycobacaterium tuberculosis synergism with fibronectin. J. Clin. Invest., 98, 1261–1268.

    Article  PubMed  CAS  Google Scholar 

  • Barnes P. F., Chatterjee D., Abrams J. S., Lu S., Want E., Yamamura M., Brennan P. J. and Modin R. L. (1992): Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J. Immunol., 149, 541–547.

    CAS  Google Scholar 

  • Barnes P. F., Lu S., Abrams J. S., Wang E., Yamamure M. and Modlin R. L. (1993): Cytokine production at the site of the disease in human tuberculosis. Infect. Immun., 61, 3482–3489.

    PubMed  CAS  Google Scholar 

  • Bogdan C., Paik J., Vodovotz Y. and Nathan C. (1992): Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor f3 and interleukin-10. J. Biol. Chem., 267, 2301–2308.

    Google Scholar 

  • Boom W. H. (1999): Gammadelta T cells and Mycobacterium tuberculosis. Microbes Infect., 1, 187–195.

    Article  PubMed  CAS  Google Scholar 

  • Byrd T. F. (1997): Tumor necrosis factor (TNF) promotes growth of Mycobacterium tuberculosis in human monocytes. Iron-mediated growth suppression is correlated with decreased release of TNF. J. Clin. Invest., 99, 2528–2529.

    Article  Google Scholar 

  • Casatella A. M. (1999): Neutrophil-derived proteins: Selling cytokines by the pound. Adv. Immunol., 73, 369–494.

    Article  Google Scholar 

  • Chan J. and Kaufman H. E. (1994): Immune mechanisms of protection. In Bloom A. S. M. (ed.): Tuberculosis: pathogenesis, protection and control. Washington, DC, 389–415.

    Google Scholar 

  • Dahl K. E., Shiratsuchi H., Hamilton B. D., Ellner J. J. and Toossi Z. (1996): Selective induction of TGF-f3 in human monocytes by lipoarabinomannan of M. tuberculosis. Infect. Immun., 64, 399–405.

    PubMed  CAS  Google Scholar 

  • Ding A., Nathan C. and Srimal S. (1990): Macrophage deactivating factor and TGF-f3 inhibit macrophage nitrogen oxide synthesis by IFN gamma. Immunology, 145, 940–945.

    CAS  Google Scholar 

  • Ehlers S., Benini J., Kutsch S., Endres R., Rietschel E. T. and Pfeffer K. (1999): Fatal granuloma necrosis without exacerbated mycobaterial growth in tumor necrosis factor receptor gene deficient mice intravenously infected with Mycobacterium avium. Infect. Immun., 67, 3571–3579.

    PubMed  CAS  Google Scholar 

  • Ellner J. J. (1997): The human response in tuberculosis. J. Infect. Dis., 176, 1351–1359.

    Article  PubMed  CAS  Google Scholar 

  • Fenhalls G., Wong A., Bezuidenhout J., van Helden P., Bardin P. and Lukey P. T. (2000): In situ production of gamma interleukin-4 and tumor necrosis factor alpha mRNA in human lung tuberculosis granulomas. Infect. Immun., 68 2827–2836.

    Google Scholar 

  • Fenton M. J., Vermeulen M. W., Kim S., Burdick M., Strieter R. M. and Kornfeld H. (1997): Induction of gamma interferon production in human alveolar macrophages by Mycobacterium tuberculosis. Infect. Immun., 65, 5149–5156.

    PubMed  CAS  Google Scholar 

  • Flynn J. L. Goldstein M. M., Chan J., Triebold K. J., Pfeffer K., Lowenstein C. J., Schreiber R., Mak T. W. and Bloom B. R. (1995): Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity, 2 561–572.

    Google Scholar 

  • Fratazzi C., Arbeit R. D., Carini C., Balcewicz-Sablinska M. K., Keane J., Kornfeld H. and Remold H. G. (1999): Macrohpage apoptosis in mycobacterial infections. J. Leukoc. Biol., 66, 763–764.

    PubMed  CAS  Google Scholar 

  • Fulton S. A., Martin T. D., Redline R. W. and Boom W. H. (2000): Pulmonary immune responses during primary Myco Calmette-Guerin bacillus infection in C57B16 mice. Am. J. Respir. Cell Mol. Biol., 22, 333–343.

    PubMed  CAS  Google Scholar 

  • Fulton S. A., Johnsen J. M., Wolf S. F., Sieberth D. S. and Boom W. H. (1996): Interleukin-12 production by human infected with Mycobacterium tuberculosis: role of phagocytosis. Infect. Immun., 64, 25–23.

    Google Scholar 

  • Garrait V., Cadranel J., Esvant H., Herry I., Morinet E, Mayaud C. and Israel-Biet D. (1997): Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV. J. Immunol., 159, 2824–2830.

    Google Scholar 

  • Hirsch C. S., Ellner J. J., Russell D. G. and Rich E. A. (1994a): Complement receptor-mediated uptake and tumor necrosis a-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol., 152, 743–749.

    PubMed  CAS  Google Scholar 

  • Hirsch C. S., Toossi Z., Othieno C., Johnson J. L., Schwander S. K., Robertson S., Wallis R.S., Edmonds K. A., Mugerwa R., Peters P. and Ellner J. J. (1999): Depressed T-cell interferon--gamma responses in pulmonary tuberculosis analysis of underlying mechanisms and modulation with therapy. J. Infect. Dis., 180, 2069–2073.

    Article  PubMed  CAS  Google Scholar 

  • Hirsch C. S., Yoneda T., Ellner J. J., Averill L. E. and Toossi Z. (1994b): Enhancement of intracellular growth of M. tuberculosis in human monocytes by transforming growth factor beta. J. Infect. Dis., 170, 1229–1237.

    Article  PubMed  CAS  Google Scholar 

  • Howard A. D. and Zwilling B. S. (1998): Cytokine production by CD4 and CD8 T cells during the growth of Mycobacterium tuberculosis in mice. Clin. Exp. Immunol., 113, 443–449.

    Article  PubMed  CAS  Google Scholar 

  • Hunter S. W., Gaylord B. E. and Brennan P. J. (1986): Structure and antigenicity of the phosophorylated lipopolysa antigens from the leprosy and tubercle bacilli. J. Biol. Chem., 261, 12345–12351.

    PubMed  CAS  Google Scholar 

  • Huygen K., Van Vooren J. P., Turneer M., Bosmans R., Dierckx P. and DeBruyn J. (1988): Specific lymphoproliferation, gamma interferon production, and serum immunoglobulin G directed against a purified 32 kDa mycobacterial protein antigen (P32) in patients with active tuberculosis. Scand. J. Immunol., 27, 187–194.

    Google Scholar 

  • Jacobs M., Brown N., Allie N. and Ryffel B. (2000): Fatal Mycobacterium bovis BCG infection in TNF LT-alpha-deficient mice. Chest, 117, 103–109.

    Article  Google Scholar 

  • Kasahara K., Sato I., Ogura K., Takeuchi H., Kobayashi K. and Adachi M. (1998): Expression of chemokines and rapid cell death in human blood neutrophils by M. tuberculosis. J. Infect. Dis., 178, 127–137.

    Article  PubMed  CAS  Google Scholar 

  • Kasahari V. M., Chen Y. Q., Su M. W., Ramirez F. and Uitto J. (1990): Tumor necrosis factor a and interferon y suppress the activation of human type I collagen gene expression by transforming growth factor 3 1. J. Clin. Invest., 86, 1489–1494.

    Article  Google Scholar 

  • Kemp K., Hviid L., Kharazmi A. and Kemp M. (1997): Interferon-gamma production by human T cells and natural killer cells in vitro in response to antigens from the two intracellular pathogens Mycobacterium tuberculosis and Leishmania major. Scand. J. Immunol., 46, 495–499.

    Article  PubMed  CAS  Google Scholar 

  • Kim S. J., Angel P., Lafyatis R. and Roberts A. B. (1990): Autoinduction of transforming growth factor 31 is mediated by the AP-1 complex. Mol. Cell Biol., 10, 1492–1495.

    PubMed  CAS  Google Scholar 

  • Kindler V., Sappino A. P, Grau G. E., Piguer P. F. and Vassalli P. (1989): The inducing role of tumor necrosis factor in the development of bacterial granulomas during BCG infection. Cell, 56, 731–740.

    Article  PubMed  CAS  Google Scholar 

  • Lawn S. D., Shattock R. J., Acheampong J. W., Lal R. B., Folks T. M., Griffin G. E. and Butera S. T. (1999): Sustained plasma TNF-alpha and HIV-1 load despite resolution of other parame- ters of immune activation during treatment of tuberculosis in Africans. AIDS, 13, 2231–2237.

    Google Scholar 

  • Lin Y., Zhang H., Gong J. and Barnes P. F. (1996): Absence of a prominent TH2 cytokine response in human tuberculosis. Infect. Immun., 64, 1351–1356.

    PubMed  CAS  Google Scholar 

  • May M. and Spagnuolo P J. (1987): Evidence for activation of the respiratory burst in the interaction of human neutrophils with M. tuberculosis. Infect. Immun., 55, 2304–2307.

    Google Scholar 

  • Mustafa T., Phyu S., Nilsen R., Jonsson R. and Bjune G. (2000): In situ expression of cytokine and cellular phenotypes in mice with slowly progressive primary tuberculosis. Scand. J. Immunol., 51, 548–556.

    Google Scholar 

  • Muthuswamy P, Hu Y. C., Carasso B., Antonio M. and Dandamudi N. (1995): Prednisone as adjunctive therapy in the management of pulmonary tuberculosis report of 12 cases and review of the literature. Chest, 107, 1621–1630.

    Article  PubMed  CAS  Google Scholar 

  • North R. J. (1995): M. tuberculosis strikingly more virulent for mice when given via the respiratory than via the intravenous route. J. Infect. Dis., 172, 1550–1553.

    Google Scholar 

  • Oppenheim J. J., Zacharie C. O. C., Mokaida N. and Matsamushima K. (1991): Properties of the novel pro-infiamma “intercine” cytokine family. Annu. Rev. Immunol., 9 617–648.

    Google Scholar 

  • Orme I. M. and Cooper A. M. (1999): Cytokine/chemokine cascades in immunity to tuberculosis. Immunol. Today, 20, 307–312.

    Article  PubMed  CAS  Google Scholar 

  • Othieno C., Hirsch C. S., Hamilton B. D., Wilkinson K., Ellner J. J. and Toossi Z. (1999): Interaction of M. tuberculosis-induced transforming growth factor [31 and interleukin 10. Infect. Immun., 67, 5730–5735.

    Google Scholar 

  • Rhoades E. R., Frank A. A. and Orme I. M. (1997): Progresion of chronic pulmonary tuberculosis in mice aerogenically infected with virulent Mycobacterium tuberculosis. Tuber. Lung Dis., 78, 57–66.

    Article  PubMed  CAS  Google Scholar 

  • Rich E. A., Torres M., Sada E., Finegan C. K., Hamilton B. D. and Toossi Z. (1997): Mycobacterium tuberculosis-stimulated expression of inducible nitric oxide synthase and production of nitric oxide by human alveolar macrophages. Tuber. Lung Dis., 78, 247–255.

    Google Scholar 

  • Riedel D. D. and Kaufmann S. H. (1997): Chemokine secretion by human polymorphonuclear granulocytes after stimulation with M. tuberculosis and lipoarabinomannan. Infect. Immun., 65, 4620–4523.

    PubMed  CAS  Google Scholar 

  • Rollins B. J. (1997): Chemokines. Blood, 90, 909–928.

    CAS  Google Scholar 

  • Rook G. A. W. and Hernandez-Pando R. (1996): The pathogenesis of tuberculosis. Annu. Rev. Microbiol., 50, 259–284.

    Article  PubMed  CAS  Google Scholar 

  • Sadek M. I., Sada E., Toossi Z., Schwander S. K. and Rich E. A. (1997): Chemokines induced by infection of mono phagocytes with M. tuberculosis and in the lungs during active pulmonary tuberculosis. Tuber. Lung Dis., 78, 247–255.

    Article  Google Scholar 

  • Schwander S. K., Sada E., Torres M., Escobedo D., Sierra J. G. and Alt Rich E. A. (1996): T lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis. J. Infect. Dis., 173, 1267–1272.

    Article  PubMed  CAS  Google Scholar 

  • Schwander S. K., Torres M., Carranza C., Escobedo D., Tary-Lehmann M., Anderson P., Toossi Z., Ellner J. J., Rich E. A. and Sada E. (2000): 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., 165, 1479–1485.

    PubMed  CAS  Google Scholar 

  • Senderovitz T. and Viskum K. (1994): Corticosteroids and tuberculosis. Res. Med., 88, 561–569.

    Article  CAS  Google Scholar 

  • Silver R. F., Li Q and Ellner J. J. (1998): Expression of virulence of Mycobacerium tuberculosis with human monocytes: virulence correlates with intracellular growth and induction of tumor necrosis factor alpha but not with evasion of lymphocyte-dependent monocyte effector functions. Infect. Immun., 66, 1190–1199.

    PubMed  CAS  Google Scholar 

  • Smith D. W., Wiegeshaus E. H., Navalkar R. and Grover A. A. (1966): Host-parasite relationships in experimental airborne tuberculosis. I. Preliminary studies in BCG-vaccinated and non-vaccinated animals. J. Bacteriol., 91, 718–724.

    PubMed  CAS  Google Scholar 

  • Snider D. E., Raviglione M. and Kochi A. (1994): Global burden of tuberculosis. In Bloom A. S. M. (ed.): Tuberculosis: pathogenesis, protection and control. Washington DC, 3–11.

    Google Scholar 

  • Solis-Herruzo J. A., Brenner D. A. and Chojkier M. (1998): Tumor necrosis factor a inhibits collagen gene transcription and collagen synthesis in cultured human fibroblasts. J. Biol. Chem., 163, 5841–5847.

    Google Scholar 

  • Sporn M. B., Roberts A. M., Wakefield L. M. and Assoian R. K. (1986): Transforming growth factor 13 biological function and chemical structure. Science, 233, 532–535.

    Article  PubMed  CAS  Google Scholar 

  • Tavares J. L., Wangoo A., Dilworth P., Marshall B., Kotecha S. and Shaw R. J. (1997): Thalidomide reduces tumor necrosis factor a alpha production by human alveolar macrophages. Respir. Med., 91, 31–39.

    Article  PubMed  CAS  Google Scholar 

  • Toossi Z. (1996): Cytokine circuits in tuberculosis. Infect. Agents Dis., 5, 98–107.

    PubMed  CAS  Google Scholar 

  • Toossi Z., Gogate P., Shiratsuchi H., Young T. and Ellner J. J. (1995): Enhanced production of transforming growth factor 3 (TGF13) by blood monocytes from patients with active tuberculosis and presence of TGF13 in tuberculosis granulomatous lung lesions. J. Immunol., 154, 465–473.

    PubMed  CAS  Google Scholar 

  • Toossi Z., Hirsch C. S., Hamilton B. D., Knuth C. K., Friedlander M. A. and Rich E. A. (1996): Decreased production of transforming growth factor 131 (TGFf31) in human alveolar macrophages. J. Immunol., 156, 3461–3468.

    PubMed  CAS  Google Scholar 

  • Toossi Z., Xia L. and Salvekar A. (1999): Transcriptional activities of human immunodeficiency virus (HIV) by Mycobacterium tuberculosis in human monocytes. Clin. Exp. Immunol., 117, 324–330.

    Article  PubMed  CAS  Google Scholar 

  • Torres M., Herrera T., Villareal H. and Sada E. (1998): Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to 30 kD antigen of Mycobacterium tuberculosis. Infect. Immun., 66, 176–180.

    PubMed  CAS  Google Scholar 

  • Tramontana J. M., Utaipat U., Molly A., Akarasewi P., Burroughs M., Makonkawkeypoon S., Johnson B., Klausner J. D., Rom W. and Kaplan G. (1995): Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol. Med., 1, 384–397.

    PubMed  CAS  Google Scholar 

  • Tsao T. C., Hong J., Huang C., Yang P., Liao S. K. and Chang K. S. (1999): Increased TNF-alpha, IL-1 beta and IL-6 levels in bronchoalveolar lavage fluid with the upregulation of their mRNA in macrophages lavaged from patients active pulmonary tuberculosis. Tuber. Lung Dis., 79, 279–285.

    Article  PubMed  CAS  Google Scholar 

  • Valone S. E., Rich E. A., Wallis R. S. and Ellner J. J. (1988): Expression of tumor necrosis factor in vitro by human mononuclear phagocytes stimulated with whole Mycobacterium bovis BCG and mycobacterial antigens. Infect. Immun., 56, 3313–3333.

    PubMed  CAS  Google Scholar 

  • Vanham G., Edmonds K. E., Qing L., Hom D., Toossi Z., Joness B., Daley C., Huebner R., Kestens L., Gigase P. and Ellner J. J. (1996): Generalized immune activation in pulmonary tuberculosis: co-activation with HIV infection. Clin. Exp. Immunol., 103, 30–34.

    Article  PubMed  CAS  Google Scholar 

  • Vicenzi E., Biswas P., Mengozzi M. and Poli G. (1997): Role of pro-inflammatory cytokines and 13-chemokines in controlling HIV replication. J. Leukoc. Biol., 62, 34–40.

    PubMed  CAS  Google Scholar 

  • Wahl S. M., Allen J. B., Weeks B. S., Wong H. L. and Klotman P. E. (1993): Transforming growth factor (3 enhances integrin expression and type IV collagenase secretion in human monocytes. Proc. Natl. Acad. Sci. USA, 90, 4577–4581.

    Article  PubMed  CAS  Google Scholar 

  • Wallis R. S., Fujiwara H. and Ellner J. J. (1996a): Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens. J. Immunol., 136, 193–196.

    Google Scholar 

  • Wallis C. C., Nsubuga R, Whalen C. C., Mugerwa R. D., Okwera A., Oette D., Jackson J. L., Johnson J. J. and Ellner J. J. (1996b): Pentoxifylline therapy in human immunodeficiency virus-serpositive persons with tuberculosis: a randomized controlled trial. J. Infect. Dis., 174, 727–733.

    Article  PubMed  CAS  Google Scholar 

  • Wallis R. S., Paranjape R. and Phillips M. (1993): Identification by two-dimensional gel electrophoresis of a 58-kilodalton tumor necrosis factor-inducing protein of Mycobacterium tuberculosis. Infect. Immun., 61, 627–632.

    Google Scholar 

  • Whalen C., Horsburgh C. R., Hom D., Lahart C., Simberkoff M. and Ellner J. J. (1995): Accelerated course of human immunodeficiency virus infection after tuberculosis. Am. J. Respir. Crit. Care Med., 151, 129–135.

    PubMed  CAS  Google Scholar 

  • Zabel A. and Ulrich Schade F. (1993): Inhibition of endogenous TNF formation by Pentoxifylline. Immunobiology, 187, 447–463.

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y., Broser M., Cohen H., Bodkin M., Law K., Reibman J. and Rom W. N. (1995): Enhanced interleukin and gene expression in macrophage after exposure to Mycobacterium tuberculosis and its comp. J. Clin. Invest., 95, 586–592.

    Article  PubMed  CAS  Google Scholar 

  • Zhu W., Downey J. S., Gu J., Di Padova F., Gram H. and Han J. (2000): Regulation of TNF expression by multiple mitogen-activated protein kinase pathways. J. Immunol., 164, 6349–6358.

    PubMed  CAS  Google Scholar 

  • Zugmaier G., Paik S., Wilding G., Knabbe C., Bano M., Lupu R., Deschauer B., Simpson S., Dickson R. B. and Lippman M. (1991): Transforming growth factor 13 1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice. Cancer Res., 51, 3590–3594.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine Case Western University, Veterans Administration Hospital, Cleveland, Ohio, USA

    Zahra Toossi

Authors
  1. Zahra Toossi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

    Andrzej Górski , Hubert Krotkiewski  & Michał Zimecki ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Toossi, Z. (2001). The Inflammatory Response in Mycobacterium Tuberculosis Infection. In: Górski, A., Krotkiewski, H., Zimecki, M. (eds) Inflammation. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9702-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-94-015-9702-9_11

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5852-2

  • Online ISBN: 978-94-015-9702-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation