Understanding the Metabolic Regulation of Immune Responses to Bacterial Infections

Project Summary/Abstract: My research program investigates how the host metabolism impacts immune responses during infection. While immune evasion strategies by bacterial virulence factors are well recognized, especially during the initiation of infection, the mechanisms by which immune responses are modulated to promote disease tolerance and pathogen persistence are less well understood. Numerous studies have shown that metabolic activities govern the function of immune cells, an emerging field called immunometabolism. Notably, upon stimulation with bacterial components, immune cells typically upregulate glycolysis to fuel inflammation and promote bacterial clearance. However, we and others have recently shown that live bacterial pathogens can manipulate the canonical glycolysis-induced inflammatory signaling to promote persistent infections. Within the next five years, we aim to deepen our mechanistic understanding of how host metabolic activities influence immune cell activation and function. Importantly, we will dissect the metabolic pathways that favor immune suppression versus activation using dietary and pharmacological interventions in our infection models. Such approaches could provide a new framework for treating a range of pathogens at diverse sites of infection, potentially transforming infection control strategies. In addition, the knowledge generated may have broader applications in inflammatory pathologies or metabolic disorders. Our research will be conducted through a multidisciplinary approach, incorporating advanced omics technologies such as next-generation transcriptomics, metabolomics, spatial metabolite imaging and indirect calorimetry, to achieve our objectives.