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

Autor: T. Mark Doherty, Markos Abebe, Lawrence Yamuah, Graham A. W. Rook, Louise Kim, Peter Andersen, Jim F. Huggett, Martha Zewdie, Alimuddin Zumla, Abebech Demissie, Abraham Aseffa, Liya Wassie, Kidist Bobosha, Howard Engers
Rok vydání: 2009
Předmět:
Zdroj: European Journal of Immunology. 40:291-301
ISSN: 0014-2980
DOI: 10.1002/eji.200939856
Popis: 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-alpha and its receptors, Fas and FasL and pro-Caspase 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-alpha 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.
Databáze: OpenAIRE
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