Human macrophage gamma interferon decreases gene expression but not replication of a Mycobacterium tuberculosis: Analysis of the host-pathogen reciprocal influence on transcription in a comparison of strains H37Rv and CMT97

Mycobacterium tuberculosis is an intracellular pathogen that readily surviv es and replicates in human macrophages (M Phi). Host cells have developed d ifferent mycobactericidal mechanisms, including the production of inflammat ory cytokines. The aim of this study was to compare the M Phi response, in terms of cytokine gene expression, to infection with the M. tuberculosis la boratory strain H37Rv and the clinical AL tuberculosis isolate CMT97. Both strains induce the production of interleukin-12 (IL-12) and IL-16 at compar able levels. However, the clinical isolate induces a significantly higher a nd more prolonged M Phi activation, as shown by reverse transcription-PCR a nalysis of IL-1 beta, IL-6, IL-10, transforming growth factor beta, tumor n ecrosis factor alpha, and gamma interferon (IFN-gamma) transcripts. Interes tingly, when IFN-gamma transcription is high, the number of M. tuberculosis genes expressed decreases and vice versa, whereas no mycobactericidal effe ct was observed in terms of bacterial growth. Expression of 11 genes was al so studied in the two Al. tuberculosis strains by infecting resting or acti vated M Phi and compared to bacterial intracellular survival. In both cases , a peculiar inverse correlation between expression of these genes and mult iplication was observed. The number and type of genes expressed by the two strains differed significantly.