ArticleInternational journal of molecular sciences2021
The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- 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
- Microglial Innate Immune Memory: Implications and Research Advances in Central Nervous System Disorders.Current issues in molecular biology · 2026Review
- Gut-derived small extracellular vesicles support trained innate immune tolerance in murine microglial cells.Frontiers in immunology · 2026Article
- Hypoxia Supports LPS-Driven Tolerance and Functional Activation in BV-2 Microglial Cells.Biology · 2025Article
- STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.Veterinary research · 2024Article
- The Vagus Nerve Regulates Immunometabolic Homeostasis in the Ovine Fetus near Term: The Impact on Terminal Ileum.Biology · 2024Article
- Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury.Frontiers in immunology · 2024Article
- Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury.Journal of neurochemistry · 2023Review
- Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator.International journal of molecular sciences · 2023Article
- Training vs. Tolerance: The Yin/Yang of the Innate Immune System.Biomedicines · 2023Review
- The role and mechanism of inflammatory response to growing rod implantation in early onset scoliosis.Frontiers in cell and developmental biology · 2023Review
- Global metabolic alterations in colorectal cancer cells during irinotecan-induced DNA replication stress.Cancer & metabolism · 2022Article
- Gut Microbiota-Derived Small Extracellular Vesicles Endorse Memory-like Inflammatory Responses in Murine Neutrophils.Biomedicines · 2022Article
- Butyrate and Metformin Affect Energy Metabolism Independently of the Metabolic Phenotype in the Tumor Therapy Model.Biomolecules · 2021Article
- Article
- LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils.International journal of molecular sciences · 2021Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.
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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.