| Autor: |
Erlich JR; Program in Chronic Infectious and Inflammatory Diseases, Oxidant and Inflammation Biology Group, School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University, Bundoora, Australia., To EE; Program in Chronic Infectious and Inflammatory Diseases, Oxidant and Inflammation Biology Group, School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University, Bundoora, Australia., Liong S; Program in Chronic Infectious and Inflammatory Diseases, Oxidant and Inflammation Biology Group, School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University, Bundoora, Australia., Brooks R; School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, Australia., Vlahos R; Program in Chronic Infectious and Inflammatory Diseases, Oxidant and Inflammation Biology Group, School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University, Bundoora, Australia., O'Leary JJ; School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, Australia.; Department of Histopathology, Trinity College Dublin, Dublin, Ireland.; Sir Patrick Dun's Laboratory, Central Pathology Laboratory, St James's Hospital, Dublin, Ireland., Brooks DA; School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, Australia.; Molecular Pathology Laboratory, Coombe Women and Infants' University Hospital, Dublin, Ireland., Selemidis S; Program in Chronic Infectious and Inflammatory Diseases, Oxidant and Inflammation Biology Group, School of Health and Biomedical Sciences, College of Science, Engineering & Health, RMIT University, Bundoora, Australia. |
| Abstrakt: |
Significance: Up until recently, metabolism has scarcely been referenced in terms of immunology. However, emerging evidence has shown that immune cells undergo an adaptation of metabolic processes, known as the metabolic switch. This switch is key to the activation, and sustained inflammatory phenotype in immune cells, which includes the production of cytokines and reactive oxygen species (ROS) that underpin infectious diseases, respiratory and cardiovascular disease, neurodegenerative disease, as well as cancer. Recent Advances: There is a burgeoning body of evidence that immunometabolism and redox biology drive infectious diseases. For example, influenza A virus (IAV) utilizes endogenous ROS production via NADPH oxidase (NOX)2-containing NOXs and mitochondria to circumvent antiviral responses. These evolutionary conserved processes are promoted by glycolysis, the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle that drive inflammation. Such metabolic products involve succinate, which stimulates inflammation through ROS-dependent stabilization of hypoxia-inducible factor-1α, promoting interleukin-1β production by the inflammasome. In addition, itaconate has recently gained significant attention for its role as an anti-inflammatory and antioxidant metabolite of the TCA cycle. Critical Issues: The molecular mechanisms by which immunometabolism and ROS promote viral and bacterial pathology are largely unknown. This review will provide an overview of the current paradigms with an emphasis on the roles of immunometabolism and ROS in the context of IAV infection and secondary complications due to bacterial infection such as Streptococcus pneumoniae . Future Directions: Molecular targets based on metabolic cell processes and ROS generation may provide novel and effective therapeutic strategies for IAV and associated bacterial superinfections. |
