Upon detection of bacterial determinants, macrophages reprogram their metabolism to clear infection. While mitochondria increase their production of oxidant species (ROS), glycolysis is upregulated to fuel synthesis of bactericidal molecules. Multiple metabolites like glucose, succinate, itaconate, lipids and lactate either accumulate or are catabolized along this process, determining the type of immune response triggered. For example, while succinate and glucose promote myeloid pro-inflammatory function, itaconate suppresses macrophage pro-oxidant activity. Several of these determinants are actively delivered to many cell compartments, like phagosomes or, for example, are released from the cell, influencing the composition of the extracellular metabolome. Recent studies suggest that opportunists like Salmonella typhimurium, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Klebsiella pneumoniae and Staphylococcus aureus induce, sense and react to these metabolites, activating multiple pathways that either potentiate or repress their virulence. When assimilated by bacteria like S. typhimurium and P. aeruginosa, succinate and itaconate not only fuel carbon flux through pro-energy routes, but also promote transcriptomic changes that modify host-pathogen interactions. K. pneumoniae senses local oxidants and reorganizes both its lipopolysaccharide and capsule architectures, which allow these organisms to evade immune activation. M. tuberculosis competes with airway macrophages for glucose and lipids, selecting for organisms that upregulate glycolytic and lipolytic routes, leading to persistence of infection. Indeed, compelling evidence suggests that S. aureus biofilm releases lactate to induce immune suppressive cytokines by modifying histone acetylation. These findings strongly suggest that bacterial metabolism is not an inert network during inflammation. Thus, host-pathogen metabolic interactions determine susceptibility to bacterial infection.
In this Research Topic, we invite researchers interested in immunometabolism to discuss how these and other relevant metabolic pathways modulate both immune defenses and bacterial disease. Submitted articles will focus on the many metabolic routes activated upon infection within host and bacteria, and how these influence adaptations of these organisms to the infected tissue. Authors will discuss how major mechanisms of bacterial pathogenesis, like biofilm and toxin production, are regulated by host metabolic components, and how different immune cell populations contribute to these phenotypes. In this new era of multi-drug resistance and limited clinical strategies to treat infections, this discussion will foster insights into new immunometabolic targets for the future design of microbicidal therapies.
We welcome the submission of Reviews (Mini Reviews, Reviews, Opinions) as well as novel Original Research articles.
Upon detection of bacterial determinants, macrophages reprogram their metabolism to clear infection. While mitochondria increase their production of oxidant species (ROS), glycolysis is upregulated to fuel synthesis of bactericidal molecules. Multiple metabolites like glucose, succinate, itaconate, lipids and lactate either accumulate or are catabolized along this process, determining the type of immune response triggered. For example, while succinate and glucose promote myeloid pro-inflammatory function, itaconate suppresses macrophage pro-oxidant activity. Several of these determinants are actively delivered to many cell compartments, like phagosomes or, for example, are released from the cell, influencing the composition of the extracellular metabolome. Recent studies suggest that opportunists like Salmonella typhimurium, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Klebsiella pneumoniae and Staphylococcus aureus induce, sense and react to these metabolites, activating multiple pathways that either potentiate or repress their virulence. When assimilated by bacteria like S. typhimurium and P. aeruginosa, succinate and itaconate not only fuel carbon flux through pro-energy routes, but also promote transcriptomic changes that modify host-pathogen interactions. K. pneumoniae senses local oxidants and reorganizes both its lipopolysaccharide and capsule architectures, which allow these organisms to evade immune activation. M. tuberculosis competes with airway macrophages for glucose and lipids, selecting for organisms that upregulate glycolytic and lipolytic routes, leading to persistence of infection. Indeed, compelling evidence suggests that S. aureus biofilm releases lactate to induce immune suppressive cytokines by modifying histone acetylation. These findings strongly suggest that bacterial metabolism is not an inert network during inflammation. Thus, host-pathogen metabolic interactions determine susceptibility to bacterial infection.
In this Research Topic, we invite researchers interested in immunometabolism to discuss how these and other relevant metabolic pathways modulate both immune defenses and bacterial disease. Submitted articles will focus on the many metabolic routes activated upon infection within host and bacteria, and how these influence adaptations of these organisms to the infected tissue. Authors will discuss how major mechanisms of bacterial pathogenesis, like biofilm and toxin production, are regulated by host metabolic components, and how different immune cell populations contribute to these phenotypes. In this new era of multi-drug resistance and limited clinical strategies to treat infections, this discussion will foster insights into new immunometabolic targets for the future design of microbicidal therapies.
We welcome the submission of Reviews (Mini Reviews, Reviews, Opinions) as well as novel Original Research articles.
