An increase in expression of a Mycobacterium tuberculosis mycolyl transferase gene (fbpB) occurs early after infection of human monocytes

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.