The lncRNA Connection Between Cellular Metabolism and Epigenetics in Trained Immunity

Fok, Ezio T.; Davignon, L.; Fanucchi, Stephanie; Mhlanga, Musa M.

doi:10.3389/fimmu.2018.03184

Cited by 49 publications

(45 citation statements)

References 84 publications

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“…Changes in glucose, glutamine and cholesterol metabolism enable maintenance and longevity of trained immunity via accumulation of immunologically active intermediate metabolites (Fok et al, 2018). Examples include: (a) cholesterol, which participates in cell membrane remodeling and increased sensitivity to subsequent stimuli, (b) succinate and fumarate, which antagonize histone demethylation and suppress antiinflammatory genes, (c) acetyl-CoA, an essential substrate for acetylating processes, and (d) NAD + which is important for epigenetic changes resulting in a switch from glucose to fatty acid oxidation during LPS-induced tolerance and sepsis-induced immune paralysis (Conti et al, 2019).…”

Section: The Role Of Immunometabolism In Bcg-induced Trained Immunitymentioning

confidence: 99%

BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny

et al. 2020

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Vaccines have been traditionally developed with the presumption that they exert identical immunogenicity regardless of target population and that they provide protection solely against their target pathogen. However, it is increasingly appreciated that vaccines can have off-target effects and that vaccine immunogenicity can vary substantially with demographic factors such as age and sex. Bacille Calmette-Guérin (BCG), the live attenuated Mycobacterium bovis vaccine against tuberculosis (TB), represents a key example of these concepts. BCG vaccines are manufactured under different conditions across the globe generating divergent formulations. Epidemiologic studies have linked early life immunization with certain BCG formulations to an unanticipated reduction (∼50%) in all-cause mortality, especially in low birthweight males, greatly exceeding that attributable to TB prevention. This mortality benefit has been related to prevention of sepsis and respiratory infections suggesting that BCG induces "heterologous" protection against unrelated pathogens. Proposed mechanisms for heterologous protection include vaccine-induced immunometabolic shifts, epigenetic reprogramming of innate cell populations, and modulation of hematopoietic stem cell progenitors resulting in altered responses to subsequent stimuli, a phenomenon termed "trained immunity." In addition to genetic differences, licensed BCG formulations differ markedly in content of viable mycobacteria key for innate immune activation, potentially contributing to differences in the ability of these diverse formulations to induce TBspecific and heterologous protection. BCG immunomodulatory properties have also sparked interest in its potential use to prevent or alleviate autoimmune and inflammatory diseases, including type 1 diabetes mellitus and multiple sclerosis. BCG can also serve as a model: nanoparticle vaccine formulations incorporating Toll-like receptor 8 agonists can mimic some of BCG's innate immune activation, suggesting that aspects of BCG's effects can be induced with non-replicating stimuli. Overall, BCG represents a paradigm for precision vaccinology, lessons from which will help inform next generation vaccines.

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Section: The Role Of Immunometabolism In Bcg-induced Trained Immunitymentioning

confidence: 99%

BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny

et al. 2020

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“…lncRNAs have only recently started to be investigated in the context of innate memory ( 34 , 35 ). lncRNA seems to facilitate the H3K4me3 epigenetic priming in innate immune cells, such as monocytes ( 34 ).…”

Section: Innate Memory and Epigenetic Reprogrammingmentioning

confidence: 99%

Induction of Innate Immune Memory by Engineered Nanoparticles in Monocytes/Macrophages: From Hypothesis to Reality

2020

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The capacity of engineered nanoparticles to activate cells of the innate immune system, in particular monocytes and macrophages, is considered at the basis of their toxic/inflammatory effects. It is, however, evident that even nanoparticles that do not directly induce inflammatory activation, and are therefore considered as safe, can nevertheless induce epigenetic modifications and affect metabolic pathways in monocytes and macrophages. Since epigenetic and metabolic changes are the main mechanisms of innate memory, we had previously proposed that nanoparticles can induce/modulate innate memory, that is, have the ability of shaping the secondary response to inflammatory challenges. In light of new data, it is now possible to support the original hypothesis and show that different types of nanoparticles can both directly induce innate memory, priming macrophages for a more potent response to subsequent stimuli, and modulate bacteria-induced memory by attenuating the priming-induced enhancement. This evidence raises two important issues. First, in addition to overt toxic/inflammatory effects, we should consider evaluating the capacity to induce innate memory and the related epigenetic and metabolic changes in the immunosafety assessment of nanomaterials, since modulation of innate memory may be at the basis of long-term unwanted immunological effects. The other important consideration is that this capacity of nanomaterials could open a new avenue in immunomodulation and the possibility of using engineered nanomaterials for improving immune responses to vaccines and resistance to infections, and modulate anomalous immune/inflammatory reactions in chronic inflammatory diseases, autoimmunity, and a range of other immune-related pathologies.

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“…Long noncoding RNAs (lncRNAs) can function as a molecular scaffold where multiple protein complexes can assemble, and they also guide these complexes to specific gene loci [30]. Recent research disclosed a new class of lncRNAs named immune gene-priming lncRNAs (IPLs), and IPLs were found to have a crucial role in the accumulation of H3K4me3 on chromatin [31].…”

Section: Mechanisms Of Trained Immunitymentioning

confidence: 99%

“…Recent research disclosed a new class of lncRNAs named immune gene-priming lncRNAs (IPLs), and IPLs were found to have a crucial role in the accumulation of H3K4me3 on chromatin [31]. A candidate IPL, termed upstream master lncRNA of the inflammatory chemokine locus (UMLILO), was found to be crucial for trained immunity; ablation of the UMLILO transcript abolished β-glucan-induced trained immunity in both human and murine monocytes [30].…”

Section: Mechanisms Of Trained Immunitymentioning

confidence: 99%

Innate Immunity and Neuroinflammation in Neuropsychiatric Conditions Including Autism Spectrum Disorders: Role of Innate Immune Memory

Jyonouchi¹

2020

Cytokines

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The neuroimmune network represents a dense network of multiple signals mediated by neurotransmitters, hormones, growth factors, and cytokines produced by multiple lineage cells and is crucial for maintaining neuroimmune homeostasis. Endogenous and exogenous stimuli, which are dangerous to the body, are detected by sensor cells, and they rapidly inform the brain through this network. Innate immunity is thought to play a major role in the neuroimmune network, through cytokines and other mediators released from secretary innate immune cells. Recent research has revealed that innate immunity has its own memory. This is accomplished by metabolic and epigenetic changes. Such changes may result in augmenting immune protection with a risk of excessive inflammatory responses to subsequent stimuli (trained immunity). Alternatively, innate immune memory can induce suppressive effects (tolerance), which may impose a risk of impaired immune defense. Innate immune memory affects the neuroimmune network for a prolonged period, and dysregulated innate immune memory has been implicated with pathogenesis of neuropsychiatric conditions. This chapter summarizes a role of innate immune memory (trained immunity vs. tolerance) in neuroinflammation in association with neuropsychiatric conditions including autism spectrum disorders (ASD).

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The lncRNA Connection Between Cellular Metabolism and Epigenetics in Trained Immunity

Cited by 49 publications

References 84 publications

BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny

BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny

Induction of Innate Immune Memory by Engineered Nanoparticles in Monocytes/Macrophages: From Hypothesis to Reality

Innate Immunity and Neuroinflammation in Neuropsychiatric Conditions Including Autism Spectrum Disorders: Role of Innate Immune Memory

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