All ETDs from UAB

Advisory Committee Chair

Adrie J C Steyn

Advisory Committee Members

Anupam Agarwal

Zdenek Hel

Louis B Justement

Chad Steele

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Despite curative treatment, tuberculosis remains a leading cause of death around the world. As such, there is great interest in novel therapeutic approaches to treat this disease. One such approach aims to enhance the efficacy of host immune cells in responding to the pathogen, Mycobacterium tuberculosis—so called host-directed therapies. The metabolism of immune cells has been a central focus in the search for hostdirected therapies, and the role of glycolysis in myeloid cells, in particular, has received much attention. However, the role of glycolysis in myeloid cells in the context of tuberculosis has not yet been made clear. Here we show that glycolysis in myeloid cells is essential for host protection in TB. We observed that mice with glycolytically deficient myeloid cells (LDHALysM-/-) are more susceptible to TB and exhibit a delayed immune response to infection with M. tuberculosis. This is associated with their inability to respond metabolically to the key antimycobacterial cytokine interferon-γ. We demonstrate that this defect can be rescued through the supplementation of pyruvate, glucogenic amino acids, or nicotinamide. Of these compounds, nicotinamide protected mice from TB in models of early and established infection. We argue that this effect is due to the enhancement of glycolysis in immune cells following treatment, and that nicotinamide should be revisited as a therapy for TB.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.