Significance of Fas and Fas ligand in tuberculous lymphadenitis

Mustafa, Tehmina; Mogga, S. J.; Mfinanga, Sayoki; Mørkve, Odd; Sviland, Lisbet

doi:10.1111/j.1365-2567.2004.02080.x

Cited by 14 publications

(16 citation statements)

References 44 publications

(70 reference statements)

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“…The prominent elevation of TNF-a and Fas/FasL expression suggests the mechanisms through which this cascade is activated and is consistent with multiple studies from human TB [38,44,[51][52][53]. These data are also consistent with the starting hypothesis that apoptosis is one of the methods used by the host for eliminating infected cells without releasing viable bacteria -and suggest that the TNF-a pathway plays an important role in this.…”

Section: Discussionsupporting

confidence: 79%

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Expression of apoptosis‐related genes in an Ethiopian cohort study correlates with tuberculosis clinical status

et al. 2009

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Mycobacterium tuberculosis remains one of the world's deadliest pathogens in part because of its ability to persist in the face of an active immune response. It has been suggested that apoptosis of infected macrophages is one way in which the host deals with intracellular pathogens and that M. tuberculosis can inhibit this process. To assess the relevance of this process for human disease, we compared the expression of multiple genes involved in the activation of the extrinsic (''death receptor initiated'') pathway of apoptosis in 29 tuberculosis patients, 70 tuberculosis contacts and 27 community controls from Ethiopia. We found that there is a strong upregulation of genes for factors that promote apoptosis in PBMC from individuals with active disease, including TNF-a and its receptors, Fas and FasL and proCaspase 8. The anti-apoptotic factor FLIP, however, was also upregulated. A possible explanation for this dichotomy was given by fractionation of PBMC using CD14, which suggests that macrophage/monocytes may regulate several key molecules differently from non-monocytic cells (especially TNF-a and its receptors, a finding confirmed by protein ELISA) potentially reducing the sensitivity to apoptotic death of monocyte/macrophages -the primary host cell for M. tuberculosis. This may represent an important survival strategy for the pathogen. IntroductionDespite vaccination and drug treatment campaigns, tuberculosis (TB) causes an estimated 8-9 million new cases and mortality of 2-3 million deaths annually [1]. The TB epidemic is largely confined to developing countries, and is particularly serious in Sub-Saharan Africa [2], where it is fanned by the HIV epidemic. Despite the high mortality, most infected people do not immediately develop active disease, but become latently infected -though they may later reactivate their disease, if they become immunocompromised [3]. It is thought that perhaps as much as a third of the world's population is latently infected, [4] Eur. J. Immunol. 2010. 40: 291-301 DOI 10.1002 Clinical immunology 291 complicating control efforts by providing a reservoir from which new cases continually arise. Understanding immunity to Mycobacterium tuberculosis, so that more effective vaccines can be developed, is thus an international priority. The response to infection with M. tuberculosis is characterized by a strong inflammatory cell-mediated immune response, with elevated expression of both and . These two cytokines are essential for controlling mycobacterial infections [11][12][13] but in most cases, M. tuberculosis survives to establish a latent infection -which can rapidly reactivate if TNF-a production is blocked [14]. The precise mechanisms involved in this process are still only poorly known. We and others have previously shown that a bias towards IL-4 expression is associated with elevated risk of disease [15] while a bias towards the IL-4 antagonist IL-4d2, or towards IFN-g, is associated with reduced pathology, a better prognosis after infection, recovery after treatment and with ...

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Section: Discussionsupporting

confidence: 79%

“…However, FasL mRNA was higher in both CD14 1 and CD14 À cells from TB patients, suggesting a broad upregulation of this molecule in this cohort. This observation is consistent with earlier reports from human and murine M. tuberculosis infections [38,40,[42][43][44]. …”

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confidence: 83%

Expression of apoptosis‐related genes in an Ethiopian cohort study correlates with tuberculosis clinical status

et al. 2009

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“…1 The apoptosis of T cell induced by Fas/FasL binding serves to downregulate the immune response. The serum FasL levels are reported to be increased in patients with various clinical conditions such as viral infections, 2,3 malaria, 4 tuberculosis, 5 and autoimmune disorders. 6 There are also reports of deranged immune activation including raised FasL levels in certain geographic areas in apparently healthy persons.…”

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“…6 There are also reports of deranged immune activation including raised FasL levels in certain geographic areas in apparently healthy persons. 5,7 During one study involving blood levels of various cytokines in neurosurgical patients, an elevated serum FasL level in some control samples (apparently healthy blood donors) was observed that was found out to be reactive for human immunodeficiency virus enzyme-linked immunosorbent assay (HIV-ELISA). This prompted us to further investigate the serum FasL levels in HIV-ELISAreactive and nonreactive blood donors.…”

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confidence: 99%

“…[2][3][4][5] Coincidentally, during the same time period, many transfusion services have acquired automated blood typing analyzers that routinely omit the conventional immediate-spin phase of the antibody screen to minimize the detection of room temperature (only)reactive "clinically insignificant" antibodies. We would like to report a case that illustrates how patients with newly formed blood group alloantibodies may be matched (and potentially transfused) with serologically incompatible red blood cells (RBCs) by the sequence of an automated antibody screen and a computer crossmatch.…”

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confidence: 99%

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Differential patterns of serum Fas ligand levels in blood donors

Verma¹,

Pandey²,

Khetan³

et al. 2008

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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

et al. 2008

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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.

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Significance of Fas and Fas ligand in tuberculous lymphadenitis

Cited by 14 publications

References 44 publications

Expression of apoptosis‐related genes in an Ethiopian cohort study correlates with tuberculosis clinical status

Expression of apoptosis‐related genes in an Ethiopian cohort study correlates with tuberculosis clinical status

Differential patterns of serum Fas ligand levels in blood donors

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

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