Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative proteomics reveals tissue-specific, infection-induced and species-specific neutrophil protein signatures – mouse bone marrow, blood and peritoneal cavity neutrophils

ABSTRACT: Neutrophils are one of the first responders to infection and are a key component of the innate immune system through their ability to phagocytose and kill invading pathogens, secrete antimicrobial molecules and produce extracellular traps. Neutrophils are produced in the bone marrow, circulate within the blood and upon immune challenge migrate to the site of infection. We wanted to understand whether this transition shapes the mouse neutrophil protein landscape, how the mouse neutrophil proteome is impacted by systemic infection and perform a comparative analysis of human and mouse neutrophils. Using quantitative mass spectrometry we reveal tissue-specific, infection-induced and species-specific neutrophil protein signatures. We show a high degree of proteomic conservation between mouse bone marrow, blood and peritoneal neutrophils, but also identify key differences in the molecules that these cells express for sensing and responding to their environment. Systemic infection triggers a change in the bone marrow neutrophil population with considerable impact on the core machinery for protein synthesis and DNA replication along with environmental sensors. We also reveal profound differences in mouse and human blood neutrophils, particularly their granule contents and their receptor repertoires. Our proteomics data provides a valuable resource for understanding neutrophil function and phenotypes across species and model systems.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Peritoneal Cavity, Neutrophil, Bone Marrow, Blood

SUBMITTER: Andrew Howden

LAB HEAD: Dr Andy Howden

PROVIDER: PXD044568 | Pride | 2024-03-13

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Quantitative proteomics reveals tissue-specific, infection-induced and species-specific neutrophil protein signatures – human blood neutrophils

Project description:Neutrophils are one of the first responders to infection and are a key component of the innate immune system through their ability to phagocytose and kill invading pathogens, secrete antimicrobial molecules and produce extracellular traps. Neutrophils are produced in the bone marrow, circulate within the blood and upon immune challenge migrate to the site of infection. We wanted to understand whether this transition shapes the mouse neutrophil protein landscape, how the mouse neutrophil proteome is impacted by systemic infection and perform a comparative analysis of human and mouse neutrophils. Using quantitative mass spectrometry we reveal tissue-specific, infection-induced and species-specific neutrophil protein signatures. We show a high degree of proteomic conservation between mouse bone marrow, blood and peritoneal neutrophils, but also identify key differences in the molecules that these cells express for sensing and responding to their environment. Systemic infection triggers a change in the bone marrow neutrophil population with considerable impact on the core machinery for protein synthesis and DNA replication along with environmental sensors. We also reveal profound differences in mouse and human blood neutrophils, particularly their granule contents and their receptor repertoires. Our proteomics data provides a valuable resource for understanding neutrophil function and phenotypes across species and model systems.

2024-03-13 | PXD044569 | Pride

Quantitative proteomics reveals tissue-specific, infection-induced and species-specific neutrophil protein signatures – Candida albicans infection experiment

2024-03-13 | PXD044556 | Pride

Human sepsis with plasma samples

Project description:The project examines the mechanisms of neutrophil dysfunction during sepsis. Our work uncovered the central role of cell free circulating histones in eliminating mature neutrophil in favour of immature cells and characterized the mechanisms that regulate their release following systemic infection. Mature and immature neutrophil Ly6Ghigh and Ly6Glow populations isolated from the spleens of WT and TCRα-deficient mice either naïve or infected with C. albicans were characterized. In addition, these populations were compared to neutrophils isolated from WT mice receiving Clodronate-liposomes and recombinant G-CSF. These studies demonstrated that T-cell derived histones drive the release of G-CSF in the spleen and progressively eliminate mature neutrophils by shortening their lifespan. Finally, we conducted proteomic analysis of plasmas isolated from patients with microbial sepsis to correlate markers of neutrophil death to plasma cytokine and histone levels, confirming the pathogenic role these molecules play during sepsis in humans.

2022-07-01 | PXD034391 | Pride

Disease-Associated SNPs From non-Coding Regions in Juvenile Idiopathic Arthritis Are Located Within or Adjacent to Functional Genomic Elements of Human Neutrophils and CD4+ T Cells [RNA-Seq]

Project description:We sequenced mRNA from 3 neutrophil cells taken from 3 male adult to generate the gene expression profile of human neutrophil cells Examination of mRNA levels in human neutrophils.

2015-06-12 | E-GEOD-66895 | biostudies-arrayexpress

Transcriptome analysis of CD16/CD62L neutrophil subsets during human experimental endotoxemia

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

Analysis of small RNAs in murine neutrophils by Solexa/Illumina genome analyzer

Project description:To examine the effects of microRNAs including miR-223 on murine neutrophil function, small RNAs cloning and sequencing from neutrophils were performed. Neutrophils were isolated from a wild-type mouse and total RNAs were prepared. Small RNAs were cloned and sequenced by Solexa/Illumina genome analyzer.

2008-07-31 | E-GEOD-12074 | biostudies-arrayexpress

Expression data from control, aged and activated neutrophils in mouse blood

Project description:Neutrophils provide immune protection against pathogens but also may promote tissue injury in inflammatory diseases. Although neutrophils are generally considered as a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and the replenishment by newly released neutrophils from the bone marrow. We used microarray to globally analyze gene expression in aged neutrophils and characterize the inflammatory programs that are activated during the aging process in the circulation. Control, aged and activated neutrophils were sorted directly from mouse blood for RNA extraction and hybridization on Affymetrix microarrays. We transfused whole blood and harvested donor neutrophils marked by the CD45.1 allele 6h later to derive neutrophils that had truly aged in vivo. Sorted neutrophils were compared to control donor neutrophils that had been transferred for only 10 min. Additionally, we harvested circulating neutrophils from TNF-? treated mice for comparison with neutrophils activated by systemic inflammation.

2015-09-24 | E-GEOD-69886 | biostudies-arrayexpress

Semi-quantitative proteomics enables mapping of global neutrophil dynamics following influenza virus infection

Project description:Lung neutrophils are causally associated with IAV-induced disease severity. Less is known about the repertoire of lethal IAV-associated neutrophil proteins or about how global changes in different neutrophil compartments are coordinated following lethal IAV infection. Here, we use semi-quantitative proteomics to characterize dynamic alterations in BM, blood and lung neutrophils at homeostasis or following a lethal IAV infection, with a secondary aim of identifying lung neutrophil-derived proteins which are selectively induced following IAV infection. Our findings identify bone marrow neutrophil maturation as the key site of anti-viral activity induction, with further upregulation or release of both anti-viral and antimicrobial effectors occurring following lung tissue infiltration.

2019-05-29 | PXD012681 | Pride

Global DNA methylation changes and differential gene expression in Anaplasma phagocytophilum-infected human neutrophils

Project description:Background: Anaplasma phagocytophilum is an obligate intracellular prokaryotic pathogen that both infects and replicates within human neutrophils. The bacterium represses multiple antimicrobial functions while simultaneously increasing proinflammatory functions by reprogramming the neutrophil genome. Previous reports show that many observed phenotypic changes are in part explained by altered gene transcription. We recently identified that large chromosomal regions of the neutrophil genome are differentially expressed during A. phagocytophilum infection. Because of this, we sought to determine whether gene expression programs altered by infection were the result of changes in the host neutrophil DNA methylome. Results: Within 24 h of infection, marked increases in DNA methylation were observed genome-wide as compared with mock-infected controls and pharmacologic inhibition of DNA methyltransferases resulted in decreased bacterial growth. New regions of DNA methylation were enriched at intron and exon junctions; however, intragenic methylation did not correlate with altered gene expression. In contrast, intergenic DNA methylation was associated with A. phagocytophilum-induced gene expression changes. Within the major histocompatibility complex locus on chromosome 6, a region with marked changes in infection-induced differential gene expression, new regions of methylation were localized to boundaries of active and inactive chromatin. Conclusions: These data strongly suggest that A. phagocytophilum infection, in addition to altering histone structure, alters DNA methylation and the epigenome of its host cell to promote survival and replication, providing evidence that such bacterial infection can radically alter the epigenome of its host cell. Examination of methylated DNA sites in 3 human donors' neutrophils with and without 24h infection by Anaplasma phagocytophilum.

2015-09-22 | E-GEOD-73228 | biostudies-arrayexpress

The porcine granulocyte proteome: expression changes in a transgenic pig model for diabetes

Project description:As transgenic INSC94Y-pigs develop a stable diabetic phenotype we were able to study the influence of elevated blood glucose levels on primary immune cells in vivo. We investigated the neutrophil proteome and compared data of transgenic animals to a control group. A total of 2371 proteins describing the whole neutrophil proteome were identified, including 396 proteins (17% of proteome) newly associated to expression in porcine neutrophils. Our studies provide novel information on the porcine granulocyte proteome and contribute to a better understanding of molecular mechanisms involved in altered immune cell function in diabetes. The data presented here is highly relevant for veterinary medicine and has translational quality for diabetes in human.

2020-06-04 | PXD017274 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data