Immunometabolic approaches to prevent, detect, and treat neonatal sepsis


The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or “training” of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.

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We thank Precision Vaccines Program graphic artist Kristin Johnson for optimizing the figure and Precision Vaccines Program Coordinator, Ms. Diana Vo, for important administrative support.

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M.G.C.: conception and design, drafting the article; A.A.: substantial contributions to conception and design, drafting the article, revising the article critically for important intellectual content; J.D.-A.: revising the article critically for important intellectual content; K.S.: revising the article critically for important intellectual content; J.L.-S.: drafting the article and revising it critically for important intellectual content; M.D.C. and O.L.: revising the article critically for important intellectual content, final approval of the version to be published.

Correspondence to Ofer Levy.

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O.L. is a named inventor on several patents relating to vaccine adjuvants.

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Conti, M.G., Angelidou, A., Diray-Arce, J. et al. Immunometabolic approaches to prevent, detect, and treat neonatal sepsis. Pediatr Res 87, 399–405 (2020).

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