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Immunology. 2006 Apr;117(4):454-62.

Immunohistochemical analysis of cytokines and apoptosis in tuberculous lymphadenitis.

Author information

1
Centre for International Health, University of Bergen, Bergen, Norway. tehmina.mustafa@cih.uib.no

Abstract

Relatively little is known about the effector mechanisms whereby the human immune system controls Mycobacterium tuberculosis infection. In this study we elaborate on the immune response and mechanisms of persistence of mycobacteria in lesions by analysing, using immunohistochemistry, the expression of cytokines [tumour necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma)], apoptotic cells and apoptosis-related proteins [Bcl2, Bax, Fas ligand (FasL) and Fas] in the human tuberculous lymphadenitis lesions. The expression of apoptosis-related proteins has been shown to be exploited by mycobacteria to evade the immune response and persist in the host. Foreign body (FB) granulomas were used as controls. In tuberculosis (TB) granulomas, epithelioid cells and multinucleated giant cells expressed cytokines differently. In epithelioid cells, the numbers of TNF-alpha-, IL-10- and TGF-beta-stained cells were higher than IFN-gamma-stained cells (P < 0.01). TGF-beta and FasL were strongly expressed in the necrotic centres as compared with other cytokines. More giant cells expressed IL-10 and TGF-beta than expressed TNF-alpha and IFN-gamma (P < 0.01). Staining of consecutive sections revealed that some giant cells expressed IL-10 but not TNF-alpha. Apoptotic TB giant cells correlated positively with the expression of TNF-alpha, IFN-gamma and TGF-beta, but not with the expression of IL-10. The percentage of giant cells expressing Bax was lower than those expressing Fas, unlike the epithelioid cells, suggesting that TB giant cells are less susceptible to apoptosis. Compared with FB giant cells, there were fewer TB giant cells showing TNF-alpha, IFN-gamma, FasL, Fas expression or undergoing apoptosis (P < 0.05). Taken together, these observations show that the cellular microenvironment of TB granulomas down-regulates microbicidal functions, favouring bacillary survival and persistence. TGF-beta and FasL may be responsible for tissue destruction. The giant cells, being less susceptible to apoptosis, may remain a continuous source of pro-inflammatory cytokines, causing immune pathology.

PMID:
16556259
PMCID:
PMC1782255
DOI:
10.1111/j.1365-2567.2005.02318.x
[Indexed for MEDLINE]
Free PMC Article

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