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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Expression of apoptosis-related genes in an Ethiopian cohort study correlates with tuberculosis clinical status
European Journal of Immunology, Volume 40, No. 1, Year 2010
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Description
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-α 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-α 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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Authors & Co-Authors
Abebe, Markos
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Denmark, Copenhagen
Statens Serum Institut
Doherty, Timothy Mark
Denmark, Copenhagen
Statens Serum Institut
Wassie, Liya
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Denmark, Copenhagen
Statens Serum Institut
Aseffa, Abraham
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Bobosha, Kidist
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Demissie, Abebech
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Zewdie, Martha
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Engers, Howard D.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Andersen, Peter Lawætz
Denmark, Copenhagen
Statens Serum Institut
Kim, Louise U.
United Kingdom, London
Ucl Medical School
Huggett, Jim
United Kingdom, London
Ucl Medical School
Rook, Graham A.W.
United Kingdom, London
Ucl Medical School
Yamuah, Lawrence K.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Zumla, A. I.
United Kingdom, London
Ucl Medical School
Fletcher, Helen A.
Unknown Affiliation
Chintu, Chifumbe Z.
Unknown Affiliation
Mulundu, Gina
Unknown Affiliation
Mwaba, Peter B.
Unknown Affiliation
McAdam, Keith P.W.J.
Unknown Affiliation
Owiafe, Patrick K.
Unknown Affiliation
Warndorff, David K.
Unknown Affiliation
Lienhardt, Christian
Unknown Affiliation
Brookes, Roger H.
Unknown Affiliation
Hill, Philip C.
Unknown Affiliation
Statistics
Citations: 30
Authors: 24
Affiliations: 3
Identifiers
Doi:
10.1002/eji.200939856
e-ISSN:
15214141
Research Areas
Cancer
Study Design
Cohort Study
Study Approach
Quantitative
Study Locations
Ethiopia