RESUMEN
Tuberculosis research spanning over a century period, has led to several important breakthroughs. These discoveries have helped in developing microbiological and molecular methods for diagnosis. Efforts on drug discovery have provided several effective anti-TB drugs that have made the treatment highly effective. However, adaptation of Mycobacterium tuberculosis and resultant drug resistance/unresponsiveness has created a challenging situation. Further, capacity of this pathogen to lie dormant in the body for years together results in a big pool of hidden disease and potential reservoir of infection. While, there is gradually improving understanding of mechanisms of dormancy, it is still patchy and not enough. Focusing on these areas will prepare us better to tackle the disease in the long run. It will be highly desirable to concentrate the scientific efforts on these grey areas of tuberculosis research.
RESUMEN
Abstract Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ) and recombinant murine interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50 ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50 ng/ml) significantly down-regulated the hspX expression. This effect was not only dependent on the concentration of the stimulus but this was time-dependent as well. A contrasting pattern of hspX expression was observed against combinations of two different concentrations of rmIFN-γ and rmIL-10. The study results suggest that rIL-10 mediated down-regulation of hspX expression, in the presence of low concentration of rIFN-γ, could be used as an important strategy to decrease the dormancy of MTB in its host and thus making MTB susceptible to the standard anti-mycobacterial therapy used for treating tuberculosis. However, as these are only preliminary results in the murine cell line model, this hypothesis needs to be first validated in human cell lines and subsequently in animal models mimicking the latent infection using clinical isolates of MTB before considering the development of modified regimens for humans.