Abstract
Approaches to the identification of metabolites have progressed from early biochemical pathway evaluation to modern high-dimensional metabolomics, a powerful tool to identify and characterize biomarkers of health and disease. In addition to its relevance to classic metabolic diseases, metabolomics has been key to the emergence of immunometabolism, an important area of study, as leukocytes generate and are impacted by key metabolites important to innate and adaptive immunity. Herein, we discuss the metabolomic signatures and pathways perturbed by the activation of the human immune system during infection and vaccination. For example, infection induces changes in lipid (e.g., free fatty acids, sphingolipids, and lysophosphatidylcholines) and amino acid pathways (e.g., tryptophan, serine, and threonine), while vaccination can trigger changes in carbohydrate and bile acid pathways. Amino acid, carbohydrate, lipid, and nucleotide metabolism is relevant to immunity and is perturbed by both infections and vaccinations. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying the host immune response. Its integration with other systems biology platforms will enhance studies of human health and disease.
Highlights
Metabolites are small molecules (50 to 1500 Daltons) produced by regulatory mechanisms and during cellular processes or acquired from exogenous sources, including diet and xenobiotics such as drugs [1]
As is the case for all the body’s cells, leukocytes use kinase, serves as an immunometabolic checkpoint in T cell development and effector responses as lipids to synthesize cell membranes and for posttranslational modifications of proteins; well as in memory T cell differentiation by regulating the metabolic switch from aerobic glycolysis to lipid metabolism is relevant to immune responses [55], including those related to epigenetic oxidative phosphorylation of lipids [54]
A plasma metabolomic analysis of immune responses to herpes zoster Zostavax vaccine demonstrated a strong association of transcriptomic pathways with multiple metabolic pathways, including lipid and amino acid (AA)
Summary
Metabolites are small molecules (50 to 1500 Daltons) produced by regulatory mechanisms and during cellular processes or acquired from exogenous sources, including diet and xenobiotics such as drugs [1]. Metabolomics can complement the characterization of complex systems measurements of the effect of a defined immune perturbation such as vaccination (Figure 1) Such an approach is promising in the newborn, given our recent demonstration of marked changes in numerous metabolic pathways across the first week of human life [47], a time of marked susceptibility to infection and of receipt of multiple vaccines, such as via the Expanded Program on Immunization—which includes Bacille Calmette–Guérin vaccine, hepatitis B vaccine, and polio vaccine) [48,49].
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