Chang-Hwa Song
Chungnam National University, Republic of Korea
Title: Endoplasmic reticulum stress-induced Calreticulin suppresses the growth of mycobacteria in macrophages
Biography
Biography: Chang-Hwa Song
Abstract
Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding chaperone protein. It is associated with the regulation of calcium homeostasis, protein folding and various cellular functions. Many diseases are associated with ER stress including tuberculosis. In this study, we examined the role of Mycobacterium tuberculosis (Mtb) induced ER stress in induction of CRT expression on macrophages. We found that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptosis. A significant increase in CRT translocation from the cytosol to the plasma membrane after 24 h of infection suggested the importance of CRT localization in the induction of apoptosis during Mtb infection. During the mycobacterial infection, production of reactive oxygen species (ROS) plays crucial roles in induction of ER stress or enhancement of proinflammatory cytokines. In the present study, we showed that pretreatment with a reactive oxygen species scavenger decreased Mtb-induced CRT expression, leading to the reduction of CHOP and caspase-3 activation. The intracellular survival of Mtb was significantly higher in macrophages transfected with a CRT-specific small interfering RNA than in control cells. The key role of CRT in inducing apoptosis included its interaction with CXCR1 and TNFR1 in Mtb-infected macrophages. The CRT/CXCR1/TNFR1 complex was shown to induce the extrinsic apoptotic pathway during Mtb infection. Collectively, our results suggest that CRT is critical for the intracellular survival of Mtb, via ER-stress-induced apoptosis