ArticleJournal of immunology (Baltimore, Md. : 1950)2006
The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn.
Article in Journal of immunology (Baltimore, Md. : 1950), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 234 citations in OpenAlex.
- In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant.Cytokine · 2016Trial
- Maturation of innate responses to mycobacteria over the first nine months of life.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine.The Journal of biological chemistry · 2013Trial
- LPS and β-Glucan Induce Differential Memory-like Inflammatory Responses with Enhanced Reactivity in Neonatal Neutrophils Compared to Adults.International journal of molecular sciences · 2026Article
- Systems biology approaches to unravelling neonatal sepsis and potential for precision diagnostics and therapeutics.Frontiers in pharmacology · 2026Review
- Reduced NLRP3, AIM2 and NLRC4 inflammasome activity in cord blood of extremely preterm infants.Frontiers in pediatrics · 2026Article
- Article
- Innovative micro physiological systems for vaccine development.Human vaccines & immunotherapeutics · 2025Review
- Partially-functional exhausted CD8+ T cells can contribute to short-term viral suppression: a computational prediction for children with perinatal HIV.bioRxiv : the preprint server for biology · 2025Article
- Article
- Sex-based differences in persistent lung inflammation following influenza infection of juvenile outbred mice.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Functional Heterogeneity of Umbilical Cord Blood Monocyte-Derived Dendritic Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Human In vitro Modeling Identifies Adjuvant Combinations that Unlock Antigen Cross-presentation and Promote T-helper 1 Development in Newborns, Adults and Elders.Journal of molecular biology · 2024Article
- Plasma adenosine deaminase-1 and -2 activities are lower at birth in Papua New Guinea than in The Gambia but converge over the first weeks of life.Frontiers in immunology · 2024Article
- The Trajectory of Successful Aging: Insights from Metagenome and Cytokine Profiling.Gerontology · 2024Article
- Impaired olfactory performance and anxiety-like behavior in a rat model of multiple sclerosis are associated with enhanced adenosine signaling in the olfactory bulb via AFrontiers in cellular neuroscience · 2024Article
- The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults.Frontiers in immunology · 2024Article
- Imbalanced Inflammatory Responses in Preterm and Term Cord Blood Monocytes and Expansion of the CD14International journal of molecular sciences · 2023Article
- Systems biological assessment of the temporal dynamics of immunity to a viral infection in the first weeks and months of life.medRxiv : the preprint server for health sciences · 2023Article
- Review: Current trends, challenges, and success stories in adjuvant research.Frontiers in immunology · 2023Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord blood monocytes demonstrate severe impairment in TNF-alpha production in response to triacylated (TLR 2/1) and diacylated (TLR 2/6) bacterial lipopeptides (BLPs). We now demonstrate that in marked contrast, BLP-induced synthesis of IL-6, a cytokine with anti-inflammatory and Th2-polarizing properties, is actually greater in neonates than adults. Remarkably, newborn blood plasma confers substantially reduced BLP-induced monocyte synthesis of TNF-alpha, while preserving IL-6 synthesis, reflecting the presence in neonatal blood plasma of a soluble, low molecular mass inhibitory factor (<10 kDa) that we identify as adenosine, an endogenous purine metabolite with immunomodulatory properties. The neonatal adenosine system also inhibits TNF-alpha production in response to whole microbial particles known to express TLR2 agonist activity, including Listeria monocytogenes, Escherichia coli (that express BLPs), and zymosan particles. Selective inhibition of neonatal TNF-alpha production is due to the distinct neonatal adenosine system, including relatively high adenosine concentrations in neonatal blood plasma and heightened sensitivity of neonatal mononuclear cells to adenosine A3 receptor-mediated accumulation of cAMP, a second messenger that inhibits TLR-mediated TNF-alpha synthesis but preserves IL-6 production. We conclude that the distinct adenosine system of newborns polarizes TLR-mediated cytokine production during the perinatal period and may thereby modulate their innate and adaptive immune responses.
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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.