About this Research Topic
Close to 1.7 billion people worldwide are asymptomatically infected with Mycobacterium tuberculosis (Mtb), the etiological agent of TB. Challenges with existing diagnostic and therapeutic intervention strategies have led to the emergence of multidrug resistance (MDR) and extensively drug-resistant (XDR) Mtb.
Immune cell function and fate have been shown to be closely linked to central metabolic pathways regulated by core signaling pathways, and the contribution of these metabolic pathways to immune cell bioenergetics has been actively studied in recent years. Given that immune activation is critically energy-dependent and that pathogens cause imbalances in metabolism, there is a gap in our knowledge on how Mtb reprograms immunometabolic pathways, rewires bioenergetics, and whether it can be reversed by host-directed therapy (HDT) to rejuvenate cellular metabolism. Furthermore, metabolism plays a fundamental role in orchestrating protective and destructive immune responses. Metabolic pathways such as glycolysis, oxidative phosphorylation (OXPHOS), glutaminolysis and fatty acid oxidation (FAO) control the functional phenotypes of immune cells and regulate the switch between quiescent and activated states in response to environmental stimuli such as pathogen-associated molecular patterns, cytokines, and chemokines. For example, distinct metabolic signatures that occur during differentiation dictate the effector status of T cells; effector T cells upregulate glycolysis and glutaminolysis to achieve maximal production of effector cytokines, whereas immunosuppressive regulatory T cells rely on FAO. Metabolism, both at the level of the single-cell and the organism, can have significant consequences for a variety of human diseases. Rapidly dividing cancer cells depend on glycolysis to sustain their energy needs in the hypoxic tumor microenvironment. Similarly, a defect in OXPHOS drives aberrant inflammation in diabetic patients. The glycolytic switch can also be hijacked by pathogens to cause disease.
The bioenergetics of infection is a new and rapidly emerging field that promises to reveal novel treatment strategies targeting common metabolic pathways of a wide variety of infectious diseases. However, to achieve this goal, there is a need to first understand both host and pathogen energy requirements as well as alternative metabolic pathways that may factor in the response to immune pressure. Unfortunately, the metabolic and bioenergetic mechanisms required for protection against mycobacterial infections are still unknown.
The goal of this Research Topic is to highlight current knowledge and research trends of TB immunometabolism and bioenergetics in the context of in vitro and ex vivo studies, animal model systems, clinical studies, and to update ongoing and future immunometabolic strategies for the control of TB. The ultimate goal is to identify both host and pathogen metabolic pathways or alterations in metabolism that can be targeted therapeutically in the treatment of TB and other mycobacterial diseases. We welcome the submission of Original Research, Review, Mini-Review, and Opinion articles that cover different aspects of mycobacterial bioenergetics, host bioenergetics, and immunometabolism, which include, but are not limited to:
1. How Mtb subverts host metabolism and bioenergetics of immune cells such as macrophages, dendritic cells, neutrophils, lymphocytes, etc.
2. Mtb virulence determinants that rewire host metabolism and bioenergetics.
3. Host directed therapies (e.g. metformin) for the control of Mtb.
4. Host bioenergetics and/or energy metabolism in clinical TB studies.
5. How anti-TB drugs modulate the bioenergetics of the host or the bacillus.
Immune cell function and fate have been shown to be closely linked to central metabolic pathways regulated by core signaling pathways, and the contribution of these metabolic pathways to immune cell bioenergetics has been actively studied in recent years. Given that immune activation is critically energy-dependent and that pathogens cause imbalances in metabolism, there is a gap in our knowledge on how Mtb reprograms immunometabolic pathways, rewires bioenergetics, and whether it can be reversed by host-directed therapy (HDT) to rejuvenate cellular metabolism. Furthermore, metabolism plays a fundamental role in orchestrating protective and destructive immune responses. Metabolic pathways such as glycolysis, oxidative phosphorylation (OXPHOS), glutaminolysis and fatty acid oxidation (FAO) control the functional phenotypes of immune cells and regulate the switch between quiescent and activated states in response to environmental stimuli such as pathogen-associated molecular patterns, cytokines, and chemokines. For example, distinct metabolic signatures that occur during differentiation dictate the effector status of T cells; effector T cells upregulate glycolysis and glutaminolysis to achieve maximal production of effector cytokines, whereas immunosuppressive regulatory T cells rely on FAO. Metabolism, both at the level of the single-cell and the organism, can have significant consequences for a variety of human diseases. Rapidly dividing cancer cells depend on glycolysis to sustain their energy needs in the hypoxic tumor microenvironment. Similarly, a defect in OXPHOS drives aberrant inflammation in diabetic patients. The glycolytic switch can also be hijacked by pathogens to cause disease.
The bioenergetics of infection is a new and rapidly emerging field that promises to reveal novel treatment strategies targeting common metabolic pathways of a wide variety of infectious diseases. However, to achieve this goal, there is a need to first understand both host and pathogen energy requirements as well as alternative metabolic pathways that may factor in the response to immune pressure. Unfortunately, the metabolic and bioenergetic mechanisms required for protection against mycobacterial infections are still unknown.
The goal of this Research Topic is to highlight current knowledge and research trends of TB immunometabolism and bioenergetics in the context of in vitro and ex vivo studies, animal model systems, clinical studies, and to update ongoing and future immunometabolic strategies for the control of TB. The ultimate goal is to identify both host and pathogen metabolic pathways or alterations in metabolism that can be targeted therapeutically in the treatment of TB and other mycobacterial diseases. We welcome the submission of Original Research, Review, Mini-Review, and Opinion articles that cover different aspects of mycobacterial bioenergetics, host bioenergetics, and immunometabolism, which include, but are not limited to:
1. How Mtb subverts host metabolism and bioenergetics of immune cells such as macrophages, dendritic cells, neutrophils, lymphocytes, etc.
2. Mtb virulence determinants that rewire host metabolism and bioenergetics.
3. Host directed therapies (e.g. metformin) for the control of Mtb.
4. Host bioenergetics and/or energy metabolism in clinical TB studies.
5. How anti-TB drugs modulate the bioenergetics of the host or the bacillus.
Keywords: TB, Bioenergetics, Energy Metabolism, Mycobacterium, Immunometabolism, Glycolysis, OXPHOS
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