Gene Silencing of Toll-like Receptor ۲ Gene Expression as a Tactic to Control Mycobacterium Tuberculosis and Granuloma Formation

Mycobacterium tuberculosis (MT) is the causative agent of tuberculosis (TB) in humans. Tuberculosis is one of the top ۱۰ causes of mortality worldwide, resulting in ۱.۸ million deaths and ۱۰.۴ million new cases in ۲۰۱۶. Understanding the fundamental features of MT biology is critical to the eradication of MT in the future. Due to the increasing frequency of antimicrobial treatment resistance and problems in vaccine development, the pathogenesis of TB for its survival and growth is highly dependent on host lipids and stimulated-lipid droplets formation. Toll-like receptor ۲ (TLR۲) forms heterophilic dimers with TLR۱ and TLR۶, therefore, recognizing many MT components. Both of these receptors identify the invading antigen and activate downstream protein kinases. Some studies demonstrated that the cyclooxygenase-۲ (COX-۲) promoter-driven gene expression includes connecting sites for transcription factors, such as nuclear factor-kappa B, CREB, NFAT, and c/EBPβ. The current study aimed to investigate the role of the TLR۲ receptor in positively regulating prostaglandin E۲ production in M. bovis (BCG) infected macrophages in vivo using a human monocytic cell line THP-۱. Our results revealed that MT infection triggers a time-dependent increase in COX-۲ expression via pathways involving TLR۲ receptor activation and enhances COX-۲ expression, leading to an increase in lipid droplet formation and suppression of macrophage activation.

کلیدواژه ها:

BCG ، THP-۱ cells model ، PPARγ ، TLR۲ siRNA knockdown