Variability of gene expression profiles in neutrophils from Germ-free mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE43511 | GEO | 2013/03/30
SECONDARY ACCESSION(S): PRJNA186624
REPOSITORIES: GEO
Similar Datasets
Project description:Neutrophils, key cells of the innate immune system, are responsible for preventing bacterial infections. It was already demonstrated that albeit neutrophils synthesize lower levels of protein and RNA they are able to marked change its gene expression after bacteria exposure. The absence of microbial stimulation has consequences on development of the mucosal immune system as demonstrated using germ-free mice as a model. We are interested in understanding if commensal flora induces changes in the gene expression profile of neutrophils in its site of production, the bone marrow. Total RNA obtained from isolated neutrophils from Bone Marrow from Germ-free mice and control
2013-03-30 | E-GEOD-43511 | biostudies-arrayexpress
Project description:Our group has proposed that low-density granulocytes (LDGs) play an important role in lupus pathogenesis, as they can damage endothelial cells and synthesize increased levels of proinflammatory cytokines and type I interferons. LDGs have a heightened capacity to synthesize neutrophil extracellular traps (NETs). NETs from LDGs display increased levels of bactericidal and immunostimulatory proteins, such as the cathelicidin LL37 and externalize double-stranded DNA (dsDNA). Lupus netting LDGs have increased capacity to kill endothelial cells and expose IL-17. Through NETosis, lupus neutrophils stimulate plasmacytoid DCs to synthesize IFN-?. Our results further expand the potential pathogenic role of aberrant lupus neutrophils through a NET-mediated effect. We used microarrays to analyze the gene expression of neutrophils in healthy and lupus patients, and of low-density granulocytes in lupus patients. Human neutrophils and LDGs were isolated from PBMCs. RNA from healthy neutrophils, lupus neutrophils and lupus LDGs was extracted and processed for hybridization on Affymetrix microarrays.
2011-06-22 | E-GEOD-26975 | biostudies-arrayexpress
Project description:Our group has proposed that low-density granulocytes (LDGs) play an important role in lupus pathogenesis, as they can damage endothelial cells and synthesize increased levels of proinflammatory cytokines and type I interferons. LDGs have a heightened capacity to synthesize neutrophil extracellular traps (NETs). NETs from LDGs display increased levels of bactericidal and immunostimulatory proteins, such as the cathelicidin LL37 and externalize double-stranded DNA (dsDNA). Lupus netting LDGs have increased capacity to kill endothelial cells and expose IL-17. Through NETosis, lupus neutrophils stimulate plasmacytoid DCs to synthesize IFN-α. Our results further expand the potential pathogenic role of aberrant lupus neutrophils through a NET-mediated effect. We used microarrays to analyze the gene expression of neutrophils in healthy and lupus patients, and of low-density granulocytes in lupus patients.
2011-06-22 | GSE26975 | GEO
Project description:It was previously demonstrated that myeloid cells assume a distinct transcriptional profile when infiltrating the brain during chronic inflammation. We demonstrated that neutrophils infiltrate the brain during pancreatic cancer. To determine if the transcriptional profile of brain-infiltrating neutrophils is distinct from those infiltrating other organs, we compared the gene signatures of brain-infiltrating neutrophils, circulating neutrophils, liver-infiltrating neutrophils, and tumor-infiltrating neutrophils to that of circulating neutrophils from healthy mice.
2020-05-08 | GSE150061 | GEO
Project description:Little is known about how commensal colonization controls neutrophil differentiation and functions. Using system immunology approaches we discovered commensal and infection induced changes in neutrophil proteomes. The identified differentially expressed genes were CRISPRed out in immortalized neutrophil progenitor cell lines transduced with lenti-guides. Analysis of maturation and bactericidal capacity of the generated CRISPRed clones ascribed a function to a currently unknown protein-termed Prenylcysteine oxidase 1 like (Pcyox1l). Pcyox1l deficient neutrophils show dramatic defects in longevity, autophagy, and bactericidal functions associated with reductions in SerpinB1a transcripts and protein. Metabolic labeling experiments revealed that Pcyox1l controls levels of protein prenylation, highlighting its key enzymatic function. The Pcyox1l deficiency phenotype is phenocopied by SerpinB1a deficiency in neutrophils signifying linked mechanisms. Commensal colonization increases Pcyox1l and SerpinB1a levels in polymorphonuclear leukocytes (PMNs) in specific pathogen free (SPF) mice when compared to germ free (GF) mice and, conversely, Pcyox1l KO mice demonstrated altered commensal microbiome and elevated susceptibility to bacterial infection. Cumulatively, our data highlight a novel metabolic pathway which is controlled by commensal colonization and governs neutrophil functionality, longevity, and bactericidal properties. In lieu with the impairment of neutrophil bactericidal functions, Pcyox1l KO mice showed elevated susceptibility to infection with the Gram-negative pathogen Pseudomonas aeruginosa
2023-03-04 | PXD030922 | Pride
Project description:We extracted RNA from C57BL/6 mouse neutrophils to measure inter-individual variability in gene expression. 5 of the 10 blood samples were analyzed separately, the other 5 were pooled then split into 5 technical replicates to measure technical variability. We could then measure inter-individual variability in gene expression and compare it to the amplitude of miRNA-guided repression by miR-223.
2016-09-21 | GSE59549 | GEO
Project description:We used an ex vivo system of murine ER-Hoxb8 neutrophils that phenotypically and morphologically recapitulate neutrophil maturation stages during five days of in vitro culture in the presence of G-CSF. To investigate the development of the ROS system in neutrophils during their development, we compared transcriptomes of D0, D1, D3 and D5 Hoxb8 neutrophils.
2020-09-15 | GSE147910 | GEO
Project description:The establishment of bacterial infections at epithelial surfaces is determined by the balance of virulence attributes of the pathogen with the activity of innate host defenses. Polymorphonuclear leukocytes (PMN) are key responders in many bacterial infections, but the mechanisms by which pathogens subvert these early responses to establish infection are largely undefined. Here, we model these early interactions between human PMN and the primary cause of urinary tract infections, namely uropathogenic Escherichia coli (UPEC). Our objective was to define virulence phenotypes of uropathogens (as compared with laboratory and commensal E. coli strains) that permit evasion of PMN activity. We found that UPEC strains resist phagocytic killing and dampen the production of antimicrobial reactive oxygen species by PMNs. Analysis of the global transcriptional responses of PMN to E. coli strains revealed that UPEC exposure downregulates the expression of PMN genes involved in proinflammatory signaling and PMN chemotaxis, adhesion, and migration. Consistent with these data, UPEC attenuated transepithelial neutrophil recruitment in an in vitro model of acute infection. We propose that these UPEC strategies are important in the establishment of epithelial infection, and that the findings are germane to a range of bacterial infections at epithelial surfaces. We used microarrays to detail the global program of gene expression in human neutrophils in response to a uropathogenic bacteria compared to a closely related non-pathogenic strain relative to control samples with no bacteria. Our goal was to elucidate a pathogen-specific response. We chose an early time point of 60 minutes to evaluate the accute response to infection. Human neutrophils were exposed to pathogenic or commensal Escherichia coli for RNA extraction and hybridization on Affymetrix microarrays
2010-03-07 | E-GEOD-18810 | biostudies-arrayexpress
Project description:The intestinal microbiota modulates host physiology and gene expression via mechanisms that are not fully understood. A recently discovered layer of gene expression regulation is N6-methyladenosine (m6A) and N6,2′ -O-dimethyladenosine (m6Am) modifications of mRNA. To unveil if these epitranscriptomic marks are affected by the gut microbiota, we performed methylated RNA-immunoprecipitation and sequencing (MeRIP-seq) to examine m6A-modifications in transcripts of mice displaying either a conventional, or a modified, or no gut microbiota and discovered that the microbiota has a strong influence on m6A- modifications in the cecum, and also, albeit to a lesser extent, in the liver, affecting pathways related to metabolism, inflammatory and antimicrobial responses . We furthermore analysed expression levels of several known writer and eraser enzymes and found the methyltransferase Mettl16 to be downregulated in absence of a microbiota. As a consequence, one of its targets, the S-adenosyl methionine synthase Mat2a was less expressed in mice without gut flora. We furthermore show that distinct commensal bacteria, Akkermansia muciniphila, Lactobacillus plantarum can affect specific m6A modifications. Together, we report here epitranscriptomic modifications as an additional level of interaction in the complex interplay between commensal bacteria and their host.
2020-02-17 | PXD016099 | Pride
Project description:Monocytes and neutrophils are both myeloid cells that have the same progenitor, the granulocyte macrophage precursor (GMP). Neutrophils are mature innate cells that are phagocytes and can degranulate to mount an immune response, whereas monocytes are immature pluripotent cells that can differentiate into macrophages and dendritic cells that can phagocytose and present antigen. To compare the expression pattern and validate samples purity by comparing expression data with previously generated data for monocytes and neutrophils, we isolated monocytes (CD45+ CD64+ CD14+ CD16-) and neutrophils (CD66b+ CD16+) from eight healthy volunteers.
2014-03-20 | E-MTAB-1573 | biostudies-arrayexpress