Glucose Metabolic Reprogramming of Macrophages Against Mycobacterium tuberculosis Infection

Tianhui Liu,1,* Zeliang Yang,2,* Jing Tong,1 Mengqiu Gao,1 Yu Pang2 1Department of Tuberculosis II, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengqiu Gao, Department of Tuberculosis II, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China, Email gaomqwdm@aliyun.com Yu Pang, Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China, Email pangyupound@163.comAbstract: Tuberculosis (TB) is a global infectious disease caused by Mycobacterium tuberculosis (Mtb). Serving as the primary effector cells, macrophages play a crucial role in host immune responses against Mtb. During Mtb infection, macrophages undergo extensive metabolic reprogramming, notably glycolysis, the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, to adapt to the challenges posed by the pathogen, with glucose metabolic rewiring being particularly critical. This review focuses on the dynamic reprogramming of glucose metabolism in macrophages during Mtb infection, highlighting how metabolic adjustments influence the activation state, polarization, and functional capacity of macrophages. Furthermore, we explore the role of glucose metabolic reprogramming in shaping the immune responses against Mtb, particularly its contribution to granuloma formation and maintenance. By understanding the intricate interplay between metabolic rewiring and immune function, we discuss the therapeutic potential of targeting glucose metabolic pathways in macrophages as a novel strategy for TB treatment. Overall, this review emphasizes the need for a deeper understanding of the relationship between glucose metabolism reprogramming and the biological function of Mtb-infected macrophages and the development of novel immunometabolic therapies—such as metformin (AMPK activator) or PKM2 modulators already used in oncology— to improve the outcomes of TB patients.Keywords: glucose metabolic reprogramming, macrophages, Mycobacterium tuberculosis