Early secreted antigenic target 6-kDa protein (ESAT6) is an essential virulence factor of Mycobacterium tuberculosis (MTb). However, ESAT6 helped fighting MTb infection according to vaccine studies. It's unclear whether ESAT6 confers protection via enhancing the innate immunity of macrophages, which are the first-line defense against MTb. We profiled the global transcriptional changes and characterized the innate immunity of THP-1 macrophages treated with ESAT6. We found ESAT6 promoted the phagocytosis ability, enhanced reactive oxygen species (ROS) generation and accelerated glucose metabolism in macrophages. Meanwhile, ESAT6 induced a distinctive phenotype of macrophages with a concurrence of pro-inflammatory and anti-inflammatory cytokines and chemokines . ESAT6 increased the expression of HIF1α mRNA and protein. Interfering HIF1α with siRNA defected the capacity of phagocytosis and ROS generation as well as glucose metabolism. Thus, ESAT6 enhanced the protective innate immunity of macrophages partially via HIF1α. This study provided clues for developing therapies against tuberculosis by targeting ESAT6.
Wenxia Sun,Shishan Yuan,Haowen Huang,Ning Liu,Yunhong Tan
A biosensor based on localized surface plasmon resonance (LSPR) was developed to detect the antibody of Mycobacterium tuberculosis using the fusion protein CFP10-ESAT6 as an antigen. To explore the diagnostic potential of the biosensor for tuberculosis (TB), the fusion protein CFP10-ESAT6 was immobilized on gold nanorods (Au NRs) by chemical modification, and the functionalized Au NRs were subsequently incubated with serums collected from TB patients, non-tuberculous pulmonary disease patients or healthy individuals. The change in the LSPR properties of Au NRs from the specific interaction between the antigen and antibody was monitored, and detection of the target antibody was completed based on the proposed biosensor. Serum analysis showed that the sensitivity of the biosensor was 79% and the specificity was 92%. Therefore, the LSPR biosensor is a valuable tool for serodiagnosis of TB.
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