ReviewFrontiers in immunology2018
Energy Demands of Early Life Drive a Disease Tolerant Phenotype and Dictate Outcome in Neonatal Bacterial Sepsis.
Review in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Harnessing the glycolysis-TCA cycle axis to boost host defense against neonatal infection.EMBO molecular medicine · 2026Article
- Interleukin-27-producing cells in gram-negative neonatal sepsis display diverse phenotypes and functions in the liver.ImmunoHorizons · 2025Article
- Infants < 90 days of age with late-onset sepsis display disturbances of the microbiome-immunity interplay.Infection · 2025Article
- Article
- Breast milk-saliva interactions in shaping early mucosal immunity.Frontiers in immunology · 2025Review
- Antibodies in breast milk: Pro-bodies designed for healthy newborn development.Immunological reviews · 2024Review
- Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy.iScience · 2024Article
- Sex Differences in Hepatic Inflammation, Lipid Metabolism, and Mitochondrial Function Following Early Lipopolysaccharide Exposure in Epileptic WAG/Rij Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Metabolic trade-offs in Neonatal sepsis triggered by TLR4 and TLR1/2 ligands result in unique dysfunctions in neural breathing circuits.Brain, behavior, and immunity · 2024Article
- New Insights in Immunometabolism in Neonatal Monocytes and Macrophages in Health and Disease.International journal of molecular sciences · 2023Review
- BCG-Induced Immune Training: Interplay between Trained Immunity and Emergency Granulopoiesis.Journal of molecular biology · 2023Review
- Maternal Vaccination to Prevent Adverse Pregnancy Outcomes: An Underutilized Molecular Immunological Intervention?Journal of molecular biology · 2023Review
- Programmed and environmental determinants driving neonatal mucosal immune development.Immunity · 2023Review
- Biomaterial mediated simultaneous delivery of spermine and alpha ketoglutarate modulate metabolism and innate immune cell phenotype in sepsis mouse models.Biomaterials · 2023Article
- Identification of key biomarkers in neonatal sepsis by integrated bioinformatics analysis and clinical validation.Heliyon · 2022Article
- Glucose supply and glycolysis inhibition shape the clinical fate of Staphylococcus epidermidis-infected preterm newborns.JCI insight · 2022Article
- Challenging molecular dogmas in human sepsis using mathematical reasoning.EBioMedicine · 2022Review
- A place for neutrophils in the beneficial pathogen-agnostic effects of the BCG vaccine.Vaccine · 2022Article
- Neonatal Sepsis and Hemostasis.Diagnostics (Basel, Switzerland) · 2022Review
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bacterial sepsis is one of the leading causes of death in newborns. In the face of growing antibiotic resistance, it is crucial to understand the pathology behind the disease in order to develop effective interventions. Neonatal susceptibility to sepsis can no longer be attributed to simple immune immaturity in the face of mounting evidence that the neonatal immune system is tightly regulated and well controlled. The neonatal immune response is consistent with a "disease tolerance" defense strategy (minimizing harm from immunopathology) whereas adults tend toward a "disease resistance" strategy (minimizing harm from pathogens). One major advantage of disease tolerance is that is less energetically demanding than disease resistance, consistent with the energetic limitations of early life. Immune effector cells enacting disease resistance responses switch to aerobic glycolysis upon TLR stimulation and require steady glycolytic flux to maintain the inflammatory phenotype. Rapid and intense upregulation of glucose uptake by immune cells necessitates an increased reliance on fatty acid metabolism to (a) fuel vital tissue function and (b) produce immunoregulatory intermediates which help control the magnitude of inflammation. Increasing disease resistance requires more energy: while adults have fat and protein stores to catabolize, neonates must reallocate resources away from critical growth and development. This understanding of sepsis pathology helps to explain many of the differences between neonatal and adult immune responses. Taking into account the central role of metabolism in the host response to infection and the severe metabolic demands of early life, it emerges that the striking clinical susceptibility to bacterial infection of the newborn is at its core a problem of metabolism. The evidence supporting this novel hypothesis, which has profound implications for interventions, is presented in this review.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.