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  • 1
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Changes in the mRNA levels of two Mycobacterium tuberculosis genes (fbpB known as antigen 85B, and hspX known as Acr) were studied in infected human monocytes. Antigen 85B is an enzyme involved in cell wall biosynthesis and is also a major target of the immune response. Acr is a stress protein believed to be involved in the bacillary response to adverse conditions and in non-replicating persistence. During the first 24 h of intracellular infection, the intramonocyte 85B mRNA level increased 54-fold (P = 0.00001) and 14.6 times in comparison with the 16S ribosomal rRNA. In contrast, the Acr mRNA fell 14.3 times. Although monocyte cytokine production was very variable, the 24 h secretion of tumour necrosis factor (TNF)-α correlated with the 85B−16S RNA ratio at 24 h (r = 0.77, Pcorr 〈 0.01). Furthermore, the addition of exogenous TNF-α to cultures was associated with a twofold increase in the 85B−16S ratio and, conversely, neutralization of endogenous TNF-α reduced the ratio. As antigen 85B also induces TNF-α, the positive feedback implied by our findings suggests a previously unsuspected role for this protein in the immunopathogenesis of tuberculosis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2592
    Keywords: Mycobacterium avium (MA) ; MA complex ; AIDS ; cytokines ; interleukin-1 (IL-1) ; IL-6 ; monocytes ; tumor necrosis factor-α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pathophysiologic basis for the exuberant intracellular growth of Mycobacterium avium complex (MAC) in AIDS patients is unclear but may relate to altered expression of modulatory cytokines. Interleukin (IL)-1, IL-6, and TNF-α expression by monocytes from AIDS patients and healthy subjects (HS) stimulated with isogeneic MAC strains (SmT, smooth-transparent, virulent; SmD, smooth-domed, avirulent) was examined. Spontaneous cytokine production was not observed in patients with AIDS. MAC strains induced less IL-1α and IL-1β release in AIDS patients than HS (P 〈 0.05). The ratio of cell-associated to supernatant IL-1α also was increased in AIDS patients (P = 0.03). IL-1β mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with SmD induced more IL-1 and TNF-α release by monocytes compared to SmT. In AIDS patients, SmD also induced greater IL-6 release than SmT (P 〈 0.01). Alterations in monocyte expression and compartmentalization of the regulatory cytokines IL-1 and IL-6 may enhance bacterial replication and contribute to the patho-genesis of MAC infection in AIDS.
    Type of Medium: Electronic Resource
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