PM2.5 Mediated Alterations In The In Vitro Human Granuloma Resulting In Reactivation Of Mycobacteria

Abstract Exposure to pollutants diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. Present study was therefore designed based on the hypothesis that exposure to particulate matter pollutant PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the extraction of PM2.5, based on initial standardizations, teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMCs granuloma formed by Mycobacterium bovis BCG at MOI 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy associated mycobacterial genes, upregulation of reactivation associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, PM2.5 treatment of already established human PBMCs granuloma formed with M. bovis BCG also led to its disruption. Although, in these conditions, downregulation of dormancy associated genes was observed but there was also a decrease in the expression of reactivation associated rpfB gene without any change in the cytokine levels. Therefore, it can be inferred that in the presence of PM2.5, there is poor granuloma formation along with a change in mycobacterial gene expression characteristics of active bacilli and alteration in host immune response without any significant changes following treatment of already established granuloma with the pollutant.