The effect of neutrophil extracellular trap (NETs) on BMDMs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1118329 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To investigate the altered gene expression levels in BMDMs treated with or without NETs. Each group had a biological repeat (n=3). Results provide insight into the effect of NETs on BMDMs.
2024-11-27 | GSE268729 | GEO
Project description:Neutrophils are necessary in mamalian’s life and are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and the entire host response. The release of neutrophil extracellular DNA in innate immune cells provides specific response to bacteria and fungi. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents and activators of immune response through release of the nuclear content into the extracellular space. Although great strides have been made in dissecting cellular and molecular pathways that control NET formation, the exact molecular composition of released NETs has not been elucidated. Here, we open the field of NETOMIC studies through isolation of NETs in combination with shotgun genomics and proteomics. This study reveals the molecular composition of NETs and specific expression regions of NETs induced in a sterile inflammation system. The existence of an in vitro NET isolation model allowed for an unprecedented amount of replicability. Additional studies are needed to verify the specificity of these sequences in the context of human health and disease upon diverse neutrophil microbial challenges.
2022-10-25 | PXD016143 | Pride
Project description:Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is characterized by flares of sterile arthritis with neutrophil infiltrate and the overproduction of Interleukin (IL)-1β. The purpose of this study was to elucidate the potential role of neutrophil subsets and neutrophil extracellular traps (NETs) in the pathogenesis of PAPA. The transcriptome of PAPA normal-dense neutrophils, autologous LDGs, and healthy control normal-dense neutrophils was characterized using RNASeq. The transcriptome of a PAPA skin biopsy and a healthy control skin sample was elucidated using RNASeq.
2018-10-23 | GSE117168 | GEO
Project description:Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs). NETs trap and kill microbes but have also been linked to inflammation in atherosclerosis, arthritis, or psoriasis by unknown mechanisms. We here report that NET-associated RNA (naRNA, which was RNA-sequenced from human primary neutrophil NETs here) stimulated further NET formation in naïve PMNs via a unique TLR8-NLRP3-caspase-1-gasdermin D-dependent inflammasome pathway. Keratinocytes also responded to naRNA with expression of psoriasis-related genes (e.g. IL17, IL36) via atypical NOD2-RIPK signaling. In vivo naRNA drove skin inflammation, which was drastically ameliorated by genetic ablation of RNA sensing. The naRNA-LL37 ‘composite DAMP’ was pre-stored in resting neutrophil granules, defining sterile NETs as intentionally inflammatory webs that amplify neutrophil activation. However, the activity of the naRNA-LL37 DAMP was transient and hence supposedly self-limiting under physiological conditions. Only upon dysregulated NET release like psoriasis, TLR-NLRP3-mediated naRNA sensing may represent both potential cause of disease and new intervention target.
2024-05-06 | GSE253440 | GEO
Project description:Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. In diabetes they are increased and impair wound healing, during which inflammation normally resolves. Atherosclerosis regression, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis regression in diabetes through unresolved inflammation. Objective: To investigate in diabetes the effect of NETs on plaque macrophage inflammation and whether NETs reduction improves atherosclerosis regression. Findings: Transcriptomic profiling of plaque macrophages from NET positive and negative areas in Ldlr-/- mice revealed inflammasome and glycolysis pathway upregulation, indicating a pro-inflammatory phenotype. During atherosclerosis regression in non-diabetic mice, plaque NET content decreased. In contrast, in diabetic mouse plaques NETs were enriched and persisted after lipid-lowering. DNase1 treatment (to degrade NETs) of diabetic mice reduced plaque NETs and macrophage inflammation and improved atherosclerosis regression after lipid-lowering. Conclusions: NETs decline during atherosclerosis regression in non-diabetic mice, but persist in diabetes and impair regression by exacerbating macrophage inflammation. DNase1 reduced diabetic plaque NETs and macrophage inflammation, and restored atherosclerosis resolution after lipid-lowering, despite ongoing hyperglycemia. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid-lowering, these data suggest that NETs contribute to the increased CVD risk in this population.
2020-05-12 | GSE145200 | GEO
Project description:We performed a comparison of transcriptome between monocyte-derived dendritic cells (moDC) cultured with neutrophil extracellular traps (NETs) from healthy donors or type 1 diabetes (T1D) patients. The source of moDCs is healthy donors and T1D patients
2020-01-07 | GSE143143 | GEO
Project description:Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome
| PRJNA481348 | ENA
Project description:Neutrophil recruitment and activation are hallmarks of the prevalent inflammatory disease, periodontitis. However, the mechanisms by which neutrophils contribute to in inflammatory bone destruction remain unclear. Herein, we document that neutrophil extracellular traps (NETs) have a direct role in mediating inflammatory pathology. In an established animal model of periodontitis, we demonstrate that genetic or pharmacologic inhibition of NETs formation, or removal of NETs by DNase-Ⅰ, alleviates inflammatory bone loss in vivo. Investigating the mechanisms by which NETs drive periodontal inflammation, we find that extracellular histones have a direct role in disease progression. Consistent with findings in animal models, histones bearing classic NET-associated post-translational modifications are correlated with disease severity and are significantly elevated in local lesions and systemic circulation of patients with periodontitis. Our work reveals NETs-associated components as pathogenic mediators, potential biomarkers, and therapeutic targets for periodontitis.
2023-05-23 | GSE228021 | GEO
Project description:Neutrophil Extracellular Traps (NETs) are structures consisting of chromatin and antimicrobial molecules that are released by neutrophils during a form of regulated cell death called NETosis. NETs trap invading pathogens, promote coagulation and activate myeloid cells to produce Type I interferons (type I IFN), proinflammatory cytokines that regulate the immune system. The mechanism of NET recognition by myeloid cells is not yet clearly identified. Here we show that macrophages and other myeloid cells phagocytose NETs. Once in phagosomes, NETs translocate to the cytosol, where they activate the DNA sensor cyclic GMP-AMP synthase (cGAS) and induce type I IFN expression. cGAS recognizes the DNA backbone of NETs. Interestingly, the NET associated serine protease Neutrophil Elastase (NE) mediates the activation of the pathway. We confirmed that NETs activate cGAS in vivo. Thus, our findings identify cGAS as a major sensor of NETs, mediating the immune activation during infection and in auto-immune diseases.
2021-02-18 | PXD015579 | Pride
Project description:Neutrophils have an important role in rapid antimicrobial defenses against and resolution of urinary tract infections (UTIs). We show that a mechanism known as neutrophil extracellular trap (NET) formation is a strategy to combat pathogens in the urinary tract. Viscous aggregates that were present in human urine sediments revealed high extracellular DNA content. The DNA formed a scaffold to which antimicrobial effector proteins derived from different neutrophil subcellular compartments bound. Treatment with deoxyribonuclease I solubilized these structures. We observed massive proteolytic degradation in the NETs with apparently dominant roles for the neutrophil granule proteases elastase, proteinase 3, and cathepsin G. In a UTI case with Staphylococcus aureus as the infectious agent, high abundance of autolysins and immune evasion factors in a cell-free NET extract suggested that controlled cell wall autolysis plays a role in derailing the host immune response and allows some bacterial cells to survive following entrapment in NETs.
2017-03-31 | MSV000080847 | MassIVE