An Army Marches on Its Stomach: Metabolic Intermediates as Antimicrobial Mediators in Mycobacterium tuberculosis Infection

Abstract

The cells of the immune system are reliant on their metabolic state to launch effective responses to combat mycobacterial infections. The bioenergetic profile of the cell determines the molecular fuels and metabolites available to the host, as well as to the bacterial invader. How cells utilize the nutrients in their microenvironment-including glucose, lipids and amino acids-to sustain their functions and produce antimicrobial metabolites, and how mycobacteria exploit this to evade the immune system is of great interest. Changes in flux through metabolic pathways alters the intermediate metabolites present. These intermediates are beginning to be recognized as key modulators of immune signaling as well as direct antimicrobial effectors, and their impact on tuberculosis infection is becoming apparent. A better understanding of how metabolism impacts immunity to Mycobacterium tuberculosis and how it is regulated and thus can be manipulated will open the potential for novel therapeutic interventions and vaccination strategies.

Primary gastric tuberculosis was misdiagnosed as submucosal mass: A rare case report and review of literature

“…[6] At present, some studies have suggested that the reduction in intragastric immunity caused by the absence of lymphoid follicles in the gastric wall may also be 1 of the causes of gastric tuberculosis. [7] Most gastric tuberculosis lesions are secondary to primary tuberculosis of the lung, intestine, bone, and other parts of the body. [8] The secondary infection mechanisms of gastric tuberculosis are as follows: M tuberculosis reaches the stomach through blood circulation or lymph circulation to form the focus of tuberculosis; tuberculosis lesions of adjacent organs spread and directly penetrate or invade the stomach to form gastric tuberculosis lesions; and when gastric ulcers or gastric cancer lesions exist, the gastric mucosa is damaged, gastric acid is reduced, and the bactericidal power of gastric juice is decreased, allowing M tuberculosis to invade all layers of the stomach and form tuberculosis lesions.…”

Lactate cross-talk in host–pathogen interactions

“…Lactate, therefore, acts at multiple levels of the host-pathogen interface and further investigation is required to fully elucidate its detrimental or beneficial effects in the ability of the macrophage to clear M.tb infection, and potentially identify new host-therapeutic targets [130][131][132]. There are limited studies exploring the role of lactate in other infection settings and disease states.…”

Metabolic Regulation of Immune Responses to Mycobacterium tuberculosis: A Spotlight on L-Arginine and L-Tryptophan Metabolism

“…Minor alterations in immune cell metabolism have the potential to fundamentally change outcomes throughout Mtb infection. Changes in carbohydrate and fatty acid metabolism following Mtb infection, particularly in macrophages, have been well described and reviewed ( 5 , 118 , 123 , 124 ). Amino acids can impact cellular nutrient signaling and be utilized by immune cells in a variety of metabolic pathways.…”

“…Amino acids can impact cellular nutrient signaling and be utilized by immune cells in a variety of metabolic pathways. For example, L-glutamine can signal nutrient sufficiency through mTOR or be oxidized and converted to other energy sources like citrate, which can enter the TCA cycle or be utilized for fatty acid synthesis ( 123 ). Meanwhile, L-serine, which plays a main role in 1 carbon metabolism via the folate cycle, has been shown to support macrophage functions through mTOR activation ( 125 ).…”