Transcriptional regulation following Mycobacterium tuberculosis infection

Tumor necrosis factor alpha (TNF-Ì_å±) and nitric oxide synthase 2 (NOS2) are crucial in the control of Mycobacterium tuberculosis infection. Previous studies have shown that murine macrophages produce lower levels of TNF-Ì_å± and NOS2 following infection with pathogenic mycobacteria compared to non-pathogenic mycobacteria. Here we compare the virulent (H37Rv) and avirulent (H37Ra) isogenic strains of M. tuberculosis and their ability to activate TNF-Ì_å± and NOS2 at a transcriptional level. We determined that macrophages infected with H37Rv compared to H37Ra and M. smegmatis showed diminished TNF-Ì_å± and NOS2 promoter activity. Differences in the ability of the isogenic strains to activate the transcription factors Ets/Elk and NF-Ì_å¼B were also observed. The reduced ability of H37Rv to activate Ets/Elk correlates with diminished TNF-Ì_å± production by infected cells relative to cells infected with H37Ra. This work demonstrates that virulent M. tuberculosis is capable of modulating the host immune response at a transcriptional level.