Department of Microbiology and Physiological Systems; UMass Metabolic Network
Immunology of Infectious Disease | Microbial Physiology | Pathogenic Microbiology
The physiological functions of macrophage, which plays a central role in the pathogenesis of tuberculosis, depend on its redox state. System xc-, a cystine-glutamate transporter, which consists of xCT and CD98, influences many ROS-dependent pathways by regulating the production of the antioxidant glutathione. xCT's ability to alter this critical host redox balance by increasing the glutathione synthesis aspect of phagocyte physiology suggested that it might influence tuberculosis pathogenesis. In this study, we found that the xCT expression was increased in peripheral blood monocyte of active tuberculosis. xCT expression in macrophage was induced by Mycobacterium tuberculosis (Mtb) through TLR2/Akt- and p38-dependent signaling pathway. Importantly, xCT deficiency conferred protection against tuberculosis, as xCT knock out mice displayed increased Mtb load and reduced pulmonary pathology in lung compared to wild type mice. xCT disruption enhanced the mycobateriacidal activity of macrophage through increasing the mycothiol oxidation. Importantly, chemical inhibition of xCT with sulfasalazine, a specific xCT inhibitor that is already approved by the FDA for treatment of inflammatory bowel disease, produces similar protective effects in vivo and in vitro, indicating xCT might be a novel and useful target for host-directed TB treatment strategy.
Rights and Permissions
Citation: Oncotarget. 2016 Apr 27. doi: 10.18632/oncotarget.9052. Link to article on publisher's site
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
DOI of Published Version
immune, inflammatory, macrophage, tuberculosis, xCT
Cai, Yi; Nambi, Subhalaxmi; Sassetti, Christopher M.; Wang, Fudi; and Chen, Xinchun, "xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation" (2016). Open Access Articles. 2850.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.