ArticlePLoS computational biology2012
Network topologies and dynamics leading to endotoxin tolerance and priming in innate immune cells.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Circulating endotoxin is correlated with fatty acid binding protein 2 and leukocyte nuclear factor-κB activation in menopausal women.Scientific reports · 2025Article
- Tolerance to Lung Infection in TWIK2 KbioRxiv : the preprint server for biology · 2025Article
- Macrophage memory emerges from coordinated transcription factor and chromatin dynamics.Cell systems · 2025Article
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- Processing stimulus dynamics by the NF-κB network in single cells.Experimental & molecular medicine · 2023Review
- Constructing maps between distinct cell fates and parametric conditions by systematic perturbations.Bioinformatics (Oxford, England) · 2023Article
- Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory.International journal of molecular sciences · 2023Article
- Low-Dose Lipopolysaccharide Protects from Lethal Paramyxovirus Infection in a Macrophage- and TLR4-Dependent Process.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- NF-κB memory coordinates transcriptional responses to dynamic inflammatory stimuli.Cell reports · 2022Article
- Two Faces of Macrophages: Training and Tolerance.Biomedicines · 2021Review
- Development of Exhausted Memory Monocytes and Underlying Mechanisms.Frontiers in immunology · 2021Article
- Mathematical Modeling of Plasticity and Heterogeneity in EMT.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Single Cell RNA-Seq and Machine Learning Reveal Novel Subpopulations in Low-Grade Inflammatory Monocytes With Unique Regulatory Circuits.Frontiers in immunology · 2021Article
- Trained immunity modulates inflammation-induced fibrosis.Nature communications · 2019Article
- Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?Metabolic brain disease · 2019Review
- An enriched network motif family regulates multistep cell fate transitions with restricted reversibility.PLoS computational biology · 2019Article
- Commentary: Is the developmentally immature immune response in paediatric sepsis a recapitulation of immune tolerance?Frontiers in immunology · 2019Article
- Modeling the Bistable Dynamics of the Innate Immune System.Bulletin of mathematical biology · 2019Article
- Immunometabolic Crosstalk: An Ancestral Principle of Trained Immunity?Trends in immunology · 2019Review
- Programming and memory dynamics of innate leukocytes during tissue homeostasis and inflammation.Journal of leukocyte biology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide) or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction) and one for tolerance (inhibitor persistence). These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.
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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.