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Project description:Neutrophil activation phenotypes in healthy subjects
| PRJNA812394 | ENA
Project description:In this study, neutrophils isolated from healthy or diabetic subjects were infected with Burkholderia thailandensis E555, a variant strain with a B.pseudomallei-like capsular polysaccharide used here as a surrogate micro-organism for B. pseudomallei. At two hours post-infection, neutrophil proteins were subjected to 4-plex iTRAQ-based comparative proteomics analysis iTRAQ-based comparative proteomic analysis.
2019-05-13 | MSV000083765 | MassIVE
Project description:During systemic inflammation, different neutrophil subsets are mobilized to the blood circulation. These neutrophil subsets can be distinguished from normal circulating neutrophils (CD16bright/CD62Lbright) based on either an immature CD16dim/CD62Lbright or a CD16bright/CD62Ldim phenotype. Interestingly, the latter neutrophil subset is known to suppress lymphocyte proliferation ex vivo, but the underlying mechanism is largely unknown. We performed transcriptome analysis on the different neutrophil subsets to identify changes that are relevant for their functions. Neutrophil subsets were isolated by FACS sorting from the blood of healthy volunteers who were administered a single dose of lipopolysaccharide (LPS). The transcriptome was determined by microarray. The mobilized neutrophil subsets were characterized by specific transcriptome profiles reflecting their phase in neutrophil lifespan. Interestingly, the CD16bright/CD62Ldim suppressive neutrophils showed an interferon-induced transcriptome profile. This was confirmed by stimulation of peripheral neutrophils with IFNgamma. These cells acquired the capacity to suppress lymphocyte proliferation through the expression of programmed death ligand 1 (PD-L1). These data demonstrate that the suppressive phenotype of the neutrophil subset is induced by IFNgamma. Specific stimulation of neutrophils might have a pivotal role in regulating lymphocyte-mediated inflammation and autoimmune disease. After LPS infusion, blood was taken at t=0 and t=4 hours. Neutrophils were FACS sorted based on CD16 and CD62L expression. Gene expression of neutrophil subsets was assessed relative to t=0 as control.
2013-05-01 | E-GEOD-42358 | biostudies-arrayexpress
Project description:Neutrophil Extracellular Traps (NETs) are chromatin-derived extracellular structures that are expelled from neutrophils in response to infectious or inflammatory stimuli. NET DNA structures are decorated with proteins including histones, myeloperoxidase and neutrophil elastase. NETs are implicated in the development of auto-immunity in diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) through the externalisation of intracellular neoepitopes e.g. dsDNA and nuclear proteins in SLE and citrullinated peptides in RA. The aim of this work was to use quantitative proteomics to identify and measure NET proteins produced by neutrophils from healthy individuals, and from patients with RA and SLE.
2019-02-18 | PXD011796 | Pride
Project description:The purpose of the present study was to elucidate the exocytic events in neutrophil-mediated inflammation. Therefore, we first investigated the expression of genes implicated in these exocytic events in a cell model for neutrophils, the promyelocytic HL-60 cell line. By the addition of 1.3% DMSO during 4.5 days, these cells are differentiated into neutrophil-like dHL-60 cells. Non-differentiated cells served as control. Upon cell differentiation, we i) identified differentially expressed genes implicated in the mechanisms of vesicle transport, and ii) found some of them being upregulated. This upregulated gene expression upon DMSO-maturation points towards a functional role in these cells. Secondly, we confirmed the expression of the selected genes in human neutrophils, isolated from venous blood of 4 different donors.
2014-11-25 | E-MTAB-2107 | biostudies-arrayexpress
Project description:Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils. Lesional skin biopsies obtained from C57BL/6J WT mice or IL-1R-deficient mice at 4 hours post-infection with Staphylococcus aureus. Uninfected skin biopsies were also collected from WT and IL-1R-deficient mice.
2012-12-05 | E-GEOD-36826 | biostudies-arrayexpress
Project description:As critical executors of the immune system, neutrophils provide an immediate inflammatory response for the clearance of debris and microbes, which is essential for the protection of health. Developmentally, neutrophils and macrophages share common progenitors, whose fate is tightly controlled by transcriptional programs. Dysregulation of these programs causes severe hematological disorders, including neutropenia, neutrophilia, leukemia, and inflammatory disorders. However, the mechanisms underlying the generation of neutrophils through these programs are poorly understood. Here, we revealed that Ikzf1 and Myb were enriched in neutrophils. Overactivation of Ikzf1 promoted neutrophil generation while suppressing macrophage emergence. Conversely, the simultaneous loss of Ikzf1 and Myb, but not the individual mutations, drastically impaired neutrophil production and enlarged the macrophage pool in both zebrafish and mice. Mechanistically, Ikzf1 and Myb formed a complex that targeted irf8 and induced the expression of a long non-coding RNA (lncRNA), irf8-2, through a novel regulatory element. LncRNA irf8-2 biased neutrophil commitment by modulating irf8 dosage via Zfp36l1. The deletion of irf8-2 resulted in defective neutrophil development and enhanced macrophage production. However, a partial ratio of neutrophils and macrophages was restored when Ikzf1, Myb, and Irf8 were all compromised. Overall, our study reveals that Ikzf1 and Myb cooperatively bias neutrophil development against Irf8 via the lncRNA irf8-2 and Zfp36l. This study provides novel insights into the conserved molecular balance between neutrophil and macrophage development during myelopoiesis, with potential implications for understanding and treating myeloid disorders.
2025-09-24 | GSE306885 | GEO
Project description:We undertook an unbiased, detailed analysis of neutrophil responses in adult patients with COVID-19 and healthy controls, to determine whether distinct neutrophil phenotypes could be identified during infections compared to the healthy state. Single-cell RNA sequencing analysis of peripheral blood neutrophils from hospitalized patients with mild or severe COVID-19 disease and healthy controls revealed distinct mature neutrophil subpopulations, with relative proportions linked to disease severity. Disruption of predicted cell-cell interactions, activated oxidative phosphorylation genes, and downregulated antiviral and host defense pathway genes were observed in neutrophils obtained during severe compared to mild infections. Our findings suggest that during severe infections, there is a loss of normal regulatory neutrophil phenotypes seen in healthy subjects, coupled with the dropout of appropriate cellular interactions.
2022-10-25 | GSE216020 | GEO
Project description:Expression of the activating transcription factor 3 (ATF3) gene is induced by Toll-like receptor (TLR) signaling. In turn, ATF3 protein inhibits the expression of various TLR-driven pro-inflammatory genes. Given its counter-regulatory role in diverse innate immune responses, we defined the effects of ATF3 on neutrophilic airway inflammation in mice. ATF3 deletion was associated with increased lipopolysaccharide (LPS)-driven airway epithelia production of CXCL1, but not CXCL2, findings concordant with a consensus ATF3-binding site identified solely in the Cxcl1 promoter. Unexpectedly, ATF3-deficient mice did not exhibit increased airway neutrophilia after LPS challenge. Bone marrow chimeras revealed a specific reduction in ATF3-/- neutrophil recruitment to wild type lungs. In vitro, ATF3-/- neutrophils exhibited a profound chemotaxis defect. Global gene expression analysis identified ablated Tiam2 expression in ATF3-/- neutrophils. TIAM2 regulates cellular motility by activating Rac1-mediated focal adhesion disassembly. Notably, ATF3-/- and ATF3-sufficient TIAM2 knockdown neutrophils, both lacking TIAM2, exhibited increased focal complex area, along with excessive CD11b-mediated F-actin polymerization. Together, our data describe a dichotomous role for ATF3-mediated regulation of neutrophilic responses: inhibition of neutrophil chemokine production, but promotion of neutrophil chemotaxis. Ly6G+ neutrophils were purified by magnetic beads from WT or ATF3 KO bone marrow and RNA was immediately isolated for global gene expression using microarrays.
2014-04-05 | E-GEOD-53973 | biostudies-arrayexpress
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