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Differential expression of mycobacterial antigen MPT64, apoptosis and inflammatory markers in multinucleated giant cells and epithelioid cells in granulomas caused by Mycobacterium tuberculosis

By Tehmina Mustafa, Harald G. Wiker, Odd Mørkve and Lisbet Sviland

Abstract

The development of granulomas is a major histopathological feature of tuberculosis. Very little information is available concerning the physiology and functions of different cell types in the tuberculous granulomas. The aim of this study was to compare the epithelioid cells (ECs) and multinucleated giant cells (MGCs) in the granulomas caused by Mycobacterium tuberculosis complex organisms. Lymph node biopsies from 30 cases of lymphadenitis were studied for expression of the secreted mycobacterial protein MPT64, caspase 3 as a marker of apoptosis, apoptosis-related proteins (Fas Ligand, Fas and Bax) and inflammatory cytokines (interleukin-10, transforming growth factor-β (TGF-β), tumour necrosis factor-α and interferon-γ) by immunohistochemistry. MGCs more often contained M. tuberculosis secretory antigen MPT64 (p < 0.001) and expressed more TGF-β (p = 0.004) than ECs. The total number of apoptotic MGCs was higher than the number of apoptotic ECs (p = 0.04). Interestingly, there was a significant negative correlation between apoptosis and MPT64 expression in MGCs (r = −0.569, p = 0.003), but not in ECs, implying that the heavy antigen load would lead to inhibition of apoptosis in these cells. When compared with ECs, higher percentage of MGCs expressed Fas Ligand and Fas (p < 0.004). The role of MGCs may thus be different from surrounding ECs and these cells by virtue of higher mycobacterial antigen load, more TGF-β and reduced apoptosis may contribute towards persistence of infection

Topics: Original Article
Publisher: Springer-Verlag
OAI identifier: oai:pubmedcentral.nih.gov:2668550
Provided by: PubMed Central
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    Citations

    1. (1999). A mouse model for slowly progressive primary tuberculosis.
    2. (1990). Activation of tuberculostatic macrophage functions by gamma interferon, interleukin-4, and tumor necrosis factor.
    3. (1997). Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factoralpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.
    4. (1999). Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis.
    5. (1999). Comparative genomics of BCG vaccines by whole-genome DNA microarray.
    6. (1997). Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection.
    7. (1998). Delayed-type hypersensitivity responses to ESAT-6 and MPT64 from Mycobacterium tuberculosis in the guinea pig. Infect Immun 66:3454–
    8. (1993). Differential regulation of formation of multinucleated giant-cells from concanavalin-A-stimulated human blood monocytes by IfnGamma and Il-4.
    9. (1994). Differential T-cell responses to mycobacteriasecreted proteins distinguish vaccination with Bacille CalmetteGuerin from infection with Mycobacterium tuberculosis.
    10. (1993). Disseminated tuberculosis in interferon-gamma gene-disrupted mice.
    11. (1995). Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions.
    12. (1999). Generation of multinucleated giant cells in vitro by culture of human monocytes with Mycobacterium bovis BCG in combination with cytokine-containing supernatants.
    13. (1999). Granuloma formation is required to contain bacillus growth and delay mortality in mice chronically infected with Mycobacterium tuberculosis.
    14. (2003). Granulomas in schistosome and mycobacterial infections: a model of local immune responses.
    15. (1997). Host responses and antigens involved in protective immunity to Mycobacterium tuberculosis.
    16. (2006). Immunohistochemical analysis of cytokines and apoptosis in tuberculous lymphadenitis.
    17. (2006). Immunohistochemistry using a Mycobacterium tuberculosis complex specific antibody for improved diagnosis of tuberculous lymphadenitis.
    18. (2002). Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly progressive primary murine Mycobacterium tuberculosis infection.
    19. (1999). Increased expression of Fas ligand on Mycobacterium tuberculosis infected macrophages: a potential novel mechanism of immune evasion by Mycobacterium tuberculosis? Inflammation 23:507–521 Virchows Arch
    20. (1999). Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells. J Immunol 162:1423–1430 456 Virchows Arch
    21. (2007). Langhans giant cells from M-tuberculosis-induced human granulomas cannot mediate mycobacterial uptake.
    22. (1999). Macrophage apoptosis in mycobacterial infections.
    23. (2000). Mendelian susceptibility to mycobacterial infection in man.
    24. (1989). Modulation of cytokine production by transforming growth factor-beta.
    25. (2004). Mycobacterial adenitis: role of Mycobacterium bovis, non-tuberculous mycobacteria, HIV infection, and risk factors in
    26. (1998). Mycobacterium tuberculosis exploits the CD95/CD95 ligand system of gammadelta T cells to cause apoptosis.
    27. (2007). Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response. Clin Exp Immunol 150:105–113
    28. (2005). Significance of Fas and Fas Ligand in tuberculous lymphadenitis.
    29. (1997). T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection.
    30. (1989). The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection.
    31. (1998). The role of TGF beta in the pathogenesis of human tuberculosis.
    32. (1995). Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.
    33. (2000). Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages.

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