Human Macrophage Gamma Interferon Decreases Gene Expression but Not Replication ofMycobacterium tuberculosis: Analysis of the Host-Pathogen Reciprocal Influence on Transcription in a Comparison of Strains H37Rv and CMT97

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Abstract
Mycobacterium tuberculosisis an intracellular pathogen that readily survives and replicates in human macrophages (MΦ). Host cells have developed different mycobactericidal mechanisms, including the production of inflammatory cytokines. The aim of this study was to compare the MΦ response, in terms of cytokine gene expression, to infection with theM. tuberculosislaboratory strain H37Rv and the clinicalM. tuberculosisisolate CMT97. Both strains induce the production of interleukin-12 (IL-12) and IL-16 at comparable levels. However, the clinical isolate induces a significantly higher and more prolonged MΦ activation, as shown by reverse transcription-PCR analysis of IL-1β, IL-6, IL-10, transforming growth factor beta, tumor necrosis factor alpha, and gamma interferon (IFN-γ) transcripts. Interestingly, when IFN-γ transcription is high, the number ofM. tuberculosisgenes expressed decreases and vice versa, whereas no mycobactericidal effect was observed in terms of bacterial growth. Expression of 11 genes was also studied in the twoM. tuberculosisstrains by infecting resting or activated MΦ and compared to bacterial intracellular survival. In both cases, a peculiar inverse correlation between expression of these genes and multiplication was observed. The number and type of genes expressed by the two strains differed significantly.

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