IL-10 down-regulates the expression of survival associated gene hspX of Mycobacterium tuberculosis in murine macrophage

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 50ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50ng/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.

Mycobacterium tuberculosis Adaptation in Response to Isoniazid Treatment in a Multi-Stress System That Mimics the Host Environment

“…hspX and tgs1 are genes in the DosR regulatory system, which play a role in mycobacterial persistence and are essential for modulating cellular metabolism upon entry into and during dormancy [13,56]. hspX and tgs1 are regulated in hypoxia, multiple-stress model, macrophage infection, and dormancy [12,[57][58][59][60]. However, the role of the DosR regulatory system in virulence is model dependent [61].…”

Understanding the early host immune response against Mycobacterium tuberculosis

“…Recently, it was demonstrated that when MTB-infected macrophages are exposed to recombinant IFN-g, the gene hspX encoding sHSP16.3 is up-regulated, whereas treatment of infected macrophage with recombinant IL-10 results in down-regulation of hspX. [51]. However, the mechanism facilitating this modulation is yet to be explored.…”

Small Heat Shock Protein16.3 of Mycobacterium tuberculosis: After Two Decades of Functional Characterization

“…Presence of oxygen [11,16,17], reactive nitrogen intermediates (RNIs) [18], vitamin C [19] and ingestion of MTB by macrophages have also been reported to upregulate the expression of its gene. Recently, our group demonstrated that when MTB infected murine macrophage is treated with exogenous IFN-g and IL-10, the expression of hspX is significantly modulated [20].…”