Endothelial Cells retain inflammatory memory through chromatin remodeling II
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE299261 | GEO | 2025/11/06
REPOSITORIES: GEO
Similar Datasets
Project description:Sepsis survivors exhibit long-term endothelial dysfunction, increasing susceptibility to secondary infections such as pneumonia. To investigate the epigenetic and transcriptional basis of endothelial inflammatory memory, we employed transcriptomic profiling of primary endothelial cells exposed to inflammatory stimuli in a two-hit model. This study reveals persistent transcriptional reprogramming following IL-6 exposure and identifies a primed endothelial state that amplifies responses to secondary challenges.
2025-11-06 | GSE298859 | GEO
Project description:Sepsis survivors exhibit long-term endothelial dysfunction, increasing susceptibility to secondary infections such as pneumonia. To investigate the epigenetic and transcriptional basis of endothelial inflammatory memory, we employed transcriptomic profiling of primary endothelial cells exposed to inflammatory stimuli in a two-hit model. This study reveals persistent transcriptional reprogramming following IL-6 exposure and identifies a primed endothelial state that amplifies responses to secondary challenges.
2025-11-06 | GSE298902 | GEO
Project description:Sepsis survivors exhibit long-term endothelial dysfunction, increasing susceptibility to secondary infections such as pneumonia. To investigate the molecular basis of endothelial inflammatory memory, we performed transcriptomic profiling of lung and kidney endothelial cells isolated from a murine two-hit sepsis model. This model incorporates cecal ligation and puncture (CLP) as the primary inflammatory event, followed by a secondary intranasal challenge with Streptococcus pneumoniae.
2025-11-06 | GSE301784 | GEO
Project description:Sepsis survivors exhibit long-term endothelial dysfunction, increasing susceptibility to secondary infections such as pneumonia. To investigate the molecular basis of endothelial inflammatory memory, we performed transcriptomic profiling of lung and kidney endothelial cells isolated from a murine two-hit sepsis model. This model incorporates cecal ligation and puncture (CLP) as the primary inflammatory event, followed by a secondary intranasal challenge with Streptococcus pneumoniae.
2025-11-06 | GSE299114 | GEO
Project description:KLRG1+ CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against systemic pathogens. Upon secondary infection, these long-lived effector cells (LLECs) are incapable of forming other circulating KLRG1− memory subsets such as central and effector memory T cells. Thus, KLRG1+ memory T cells are frequently referred to as a terminally differentiated population that is relatively short lived. Here, we show that following viral infection of mice, effector cells derived from LLEC rapidly enter nonlymphoid tissues and reduce pathogen burden, but are largely dependent on receiving antigen cues from vascular endothelial cells. Single-cell RNA sequencing revealed that secondary memory cells in nonlymphoid tissues arising from either KLRG1+ or KLRG1− memory precursors developed a similar transcriptional signature. Thus, although LLEC cannot differentiate into other circulating memory populations, they still retain the flexibility to enter tissues and establish residency.
2025-03-05 | GSE261279 | GEO
Project description:Sepsis is the most common cause of hospitalization worldwide. Millions of people survive sepsis each year and are at risk for rehospitalization and death. Pulmonary complications such as respiratory failure due to pneumonia and exacerbation of chronic respiratory disease are among the most common reasons for rehospitalization in sepsis survivors. In order to prevent additional morbidity and death in patients surviving sepsis, we must establish biomarkers to identify patients at risk for pulmonary complications and develop treatments. Late complications in sepsis survivors, particularly nosocomial infections, are proposed to occur through persistent immune reprogramming after sepsis known as immunoparalysis. However, pro-inflammatory immune reprogramming in the form of primed or enhanced responses to secondary stimuli has also been described and could directly contribute to tissue injury and death. Primed immune responses and their contribution to long-term sepsis complications remains understudied. We hypothesize that primed immune responses to inflammatory stimuli in the lung after sepsis are associated with pulmonary complications in survivors of sepsis. To this end, we developed a model of antibiotic treated sepsis induced by cecal ligation and puncture followed three weeks later by secondary challenge with intranasal lipopolysaccharide to induce inflammatory lung injury. We find that mice surviving sepsis have enhanced lung injury responses in the setting of an exaggerated proinflammatory immune response, including primed Ly6Chi monocyte Tnf expression. Using RNA sequencing, we identified derangements in lung gene expression after CLP prior to LPS administration which may mediate enhanced lung injury in this model. One potential mediator, S100A8/A9, was also found to be elevated in the circulation of human sepsis survivors for up to 180 days after sepsis. These findings validate our model and identify S100A8/A9 as one of many potential biomarkers and therapeutic targets for patients at risk for long-term pulmonary complications after sepsis. The role of S100A8/A9, monocyte priming, and other factors predisposing to enhanced lung injury responses and pulmonary complications after sepsis warrant further investigation in humans and mice.
2021-06-23 | GSE168796 | GEO
Project description:Training and priming of innate immune cells involve preconditioning by PAMPs, DAMPs and/or cytokines that elicits stronger induction of inflammatory genes upon secondary challenge. Previous models distinguish training and priming based upon whether immune activation returns to baseline prior to secondary challenge. Tolerance is a protective mechanism whereby potent stimuli induce refractoriness to secondary challenge. Training and priming are important for innate memory responses that protect against infection, efficacy of vaccines, and maintaining innate immune cells in a state of readiness; tolerance prevents toxicity from excessive immune activation. Dysregulation of these processes can contribute to pathogenesis of autoimmune/inflammatory conditions, post-COVID-19 hyperinflammatory states, or sepsis- associated immunoparalysis. Training, priming and tolerance regulate similar ‘signature’ inflammatory genes such as TNF, IL6 and IL1B and utilize overlapping epigenetic mechanisms. We review how interferons (IFNs), best known for activating Jak-STAT signaling and interferon- stimulated genes, also play a key role regulating training, priming and tolerance via chromatin- mediated mechanisms. We present new data on how monocyte-to-macrophage differentiation modulates IFN-g-mediated priming, changes AP-1 and CEBP activity, and attenuates superinduction of inflammatory genes. We present a ‘training-priming continuum’ model that integrates IFN-mediated priming into current concepts about training and tolerance and proposes a central role for STAT1 and IRF1.
2024-05-22 | GSE262911 | GEO
Project description:Training and priming of innate immune cells involve preconditioning by PAMPs, DAMPs and/or cytokines that elicits stronger induction of inflammatory genes upon secondary challenge. Previous models distinguish training and priming based upon whether immune activation returns to baseline prior to secondary challenge. Tolerance is a protective mechanism whereby potent stimuli induce refractoriness to secondary challenge. Training and priming are important for innate memory responses that protect against infection, efficacy of vaccines, and maintaining innate immune cells in a state of readiness; tolerance prevents toxicity from excessive immune activation. Dysregulation of these processes can contribute to pathogenesis of autoimmune/inflammatory conditions, post-COVID-19 hyperinflammatory states, or sepsis- associated immunoparalysis. Training, priming and tolerance regulate similar ‘signature’ inflammatory genes such as TNF, IL6 and IL1B and utilize overlapping epigenetic mechanisms. We review how interferons (IFNs), best known for activating Jak-STAT signaling and interferon- stimulated genes, also play a key role regulating training, priming and tolerance via chromatin- mediated mechanisms. We present new data on how monocyte-to-macrophage differentiation modulates IFN-g-mediated priming, changes AP-1 and CEBP activity, and attenuates superinduction of inflammatory genes. We present a ‘training-priming continuum’ model that integrates IFN-mediated priming into current concepts about training and tolerance and proposes a central role for STAT1 and IRF1.
2024-05-22 | GSE262912 | GEO
Project description:More than half of all brain tumour survivors experience debilitating and often progressive cognitive decline after treatment with radiotherapy. Microglia, the tissue-resident macrophages of the brain, have been implicated in this decline. In response to various insults microglia can develop innate immune memory (IMM), which can either enhance (priming) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigated whether radiation can affect the IMM of microglia by irradiating the brains of rats and later exposing them to a second inflammatory challenge. Transcriptomic profiling of microglia isolated from irradiated rats showed a stronger immune response to a second inflammatory insult demonstrating that radiation can lead to long-lasting molecular reprogramming of microglia. Transcriptomic analysis of post-mortem non-tumour brain tissue of glioblastoma patients indicates that radiation-induced microglial priming is conserved in humans. Targeting microglial priming after radiotherapy or avoiding further inflammatory insults could decrease progressive radiotherapy-induced cognitive decline.
2024-02-19 | GSE229940 | GEO
Project description:Sepsis is defined as a systemic inflammatory response secondary to a proven or suspected infection. Mechanisms governing this inflammatory response have been shown to be complex and dynamic, involving cross-talking among diverse signaling pathways. However, current knowledge on mechanisms underlying sepsis is far from providing a complete picture of the syndrome, justifying additional efforts that might add to this scenario. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis: the analysis of gene transcription at the genome level potentially avoids results derived from biased assumptions. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor and non-survivor septic patients. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia. Global gene expression profiling allowed us to characterize early sepsis, as compared to healthy individuals. Our results corroborate literature reports on inflammation response in the early stages of sepsis but highlight great heterogeneity in gene expression during sepsis progress. Additionally, global gene expression in the early stage was also able to distinguish sepsis from septic shock and correlated with patient outcome. Differences in oxidative stress seem to be associated with clinical outcome, since significant differences in the expression profile of related genes were observed between survivors and non-survivors at the time of patient enrollment (early sepsis). However, our results substantiate current knowledge supporting that sepsis syndrome development is indeed multifaceted. Although the initial infection of enrolled patients was pneumonia, seven days later gene expression profiles seemed to be characteristic of each patient, common gene expression changes distinguishing survivors from non-survivors. This result could be associated with the underlying health status of each one of them, with complications due to sepsis itself as well as with distinct timing for response to treatment. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor (n=5) and non-survivor (n=5) septic patients, as well as from 3 healthy controls. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia.
2014-06-20 | E-GEOD-48080 | biostudies-arrayexpress