Rj. Wilkinson et al., An increase in expression of a Mycobacterium tuberculosis mycolyl transferase gene (fbpB) occurs early after infection of human monocytes, MOL MICROB, 39(3), 2001, pp. 813-821
Changes in the mRNA levels of two Mycobacterium tuberculosis genes (fbpB kn
own as antigen 85B, and hspX known as Acr) were studied in infected human m
onocytes. Antigen 85B is an enzyme involved in cell wall biosynthesis and i
s also a major target of the immune response. Acr is a stress protein belie
ved to be involved in the bacillary response to adverse conditions and in n
on-replicating persistence. During the first 24 h of intracellular infectio
n, 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 mRN
A fell 14.3 times. Although monocyte cytokine production was very variable,
the 24 h secretion of tumour necrosis factor (TNF)-alpha correlated with t
he 85B-16S RNA ratio at 24 h (r = 0.77, P-corr < 0.01). Furthermore, the ad
dition of exogenous TNF-<alpha> to cultures was associated with a twofold i
ncrease in the 85B-16S ratio and, conversely, neutralization of endogenous
TNF-alpha reduced the ratio. As antigen 85B also induces TNF-alpha, the pos
itive feedback implied by our findings suggests a previously unsuspected ro
le for this protein in the immunopathogenesis of tuberculosis.