title: Expression of apoptosis-related genes in an Ethiopian cohort study correlates with tuberculosis clinical status.
abstract: 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.
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors.forename: Markos
authors.initials: M
authors.lastname: Abebe
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Liya
authors.initials: L
authors.lastname: Wassie
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.forename: Kidist
authors.initials: K
authors.lastname: Bobosha
authors.forename: Abebech
authors.initials: A
authors.lastname: Demissie
authors.forename: Martha
authors.initials: M
authors.lastname: Zewdie
authors.forename: Howard
authors.initials: H
authors.lastname: Engers
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Louise
authors.initials: L
authors.lastname: Kim
authors.forename: Jim
authors.initials: J
authors.lastname: Huggett
authors.forename: Graham
authors.initials: G
authors.lastname: Rook
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Yamuah
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015331:Cohort Studies; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult