Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Organism-level analysis of sepsis reveals mechanisms of systemic inflammation

ABSTRACT: Organism-level analysis of sepsis reveals mechanisms of systemic inflammation

PROVIDER: PRJNA1063741 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23288100_1.fastq.gz	Fastqsanger.gz
	SRR23288100_2.fastq.gz	Fastqsanger.gz
	SRR23288101_1.fastq.gz	Fastqsanger.gz
	SRR23288101_2.fastq.gz	Fastqsanger.gz
	SRR23288401_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 498

Similar Datasets

Organism-level analysis of sepsis reveals mechanisms of systemic inflammation

Project description:Sepsis is an uncontrolled, systemic response to infection with life-threatening consequences. Our understanding of the pathogenesis of sepsis across organs of the body is rudimentary. Here, using mouse models of sepsis, we generate a dynamic, organism-wide map of the pathogenesis of the disease, revealing the spatiotemporal patterns of well-known and previously unrecognized effects of sepsis on the body. By combining functional perturbations with organism-wide profiling, we discover two interorgan mechanisms that are key to the pathophysiology of sepsis. First, we find that a hierarchical cytokine circuit arising from the pairwise effects of TNF plus IL-18, IFN-γ, or IL-1β suffices to explain a large fraction of the molecular effects of sepsis on the body. Moreover, the effects of these three cytokine pairs on the abundance of nearly two hundred cell types across nine organ types recapitulate half of all the cellular effects of sepsis. Second, we uncover an interorgan pathway whereby a gut-derived, secreted phospholipase, Pla2g5, mediates hemolysis in the blood circulation and contributes to multi-organ failure during sepsis. Thus, a simplifying principle in the systemic behavior of the cytokine network and a lipase misdirected from gut to blood provide fundamental insights to help build a unifying mechanistic framework for the pathophysiological effects of sepsis on the organ systems of the body.

2024-01-11 | GSE253061 | GEO

Organism-Wide Analysis of Sepsis Reveals Mechanisms of Systemic Inflammation

Project description:Phospholipase A2 group V (PLA2G5) is a secretory and Ca2+-dependent lipolytic enzyme and is inducible during several pathologic conditions. However, it has been unknown how PLA2G5 plays a role in sepsis. To study the role of PLA2G5 in sepsis, we performed lipidomics analysis of plasma and tissues from LPS-injected mice with or without PLA2G5 blockade. Here, we showed that PLA2G5 is involved in the production of fatty acids such as oleic acid and linoleic acid, lysophospholipids such as lysophosphatidic acid, lysophosphatidylcholine, lysophatidylethanolamine, and lysophosphatidylserine species, and metabolites derived from polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and linoleic acids during sepsis. Thus, PLA2G5 regulates selective lipid pathways during sepsis.

2023-01-23 | ST002455 | MetabolomicsWorkbench

Transcription profiling ofhuman pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum

Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.

2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress

Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

Project description:Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is secreted by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth phase-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of Escherichia coli (E. coli), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane and bacterial death notably contribute to ATP release. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analysed using a transformed E. coli bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.

2024-07-16 | GSE272296 | GEO

Expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum

2008-12-12 | GSE13904 | GEO

Secreted Phospholipase PLA2G5 Acts as a Self-Venom in Sepsis by Mediating Hemolysis

Project description:Sepsis is a systemic response to infection with life-threatening consequences such as hemolysis, a predictor of mortality risks for the disease. Here, by measuring organism-wide changes in gene expression, we discovered that the secreted phospholipase PLA2G5 is induced in colon cell types during sepsis. The genetic deletion and antibody blockade of PLA2G5 abrogated the lethal effects of sepsis. PLA2G5 blockade during sepsis led to an increase in splenic red pulp macrophages and iron homeostasis, linking PLA2G5 to red blood cell homeostasis during sepsis. Mechanistically, bloodborne PLA2G5 led to intravascular hemolysis through its lipolytic activity on red blood cell membranes. In humans with sepsis, the plasma level of PLA2G5 was elevated and predictive of disease severity and mortality. We conclude that sepsis corrupts PLA2G5 from the gut into becoming a systemic self-venom which is toxic for host red blood cells.

2024-01-11 | GSE253060 | GEO

Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

Project description:Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis

| PRJNA1136040 | ENA

The mechanisms of neutrophil dysfunction during sepsis

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.

2022-12-13 | PXD032961 | Pride

Characterization of proteome dynamics in individual vascular layers at the early stage of acute sepsis

Project description:In this study we developed a stable isotope labeled of mammals (SILAM) model coupled to the application of differential systemic decellularization in vivo (DISDIVO) to evaluate the molecular dynamics of whole organism vascular beds at the initial phase of acute sepsis. Three different vascular layers where characterized at the initial stage of sepsis, glycocalyx (GC), endothelial cells (ECs) and smooth muscle cells (SMCs).

2020-10-29 | PXD018274 | Pride

A pairwise cytokine code explains the organism-wide response to sepsis

Project description:A pairwise cytokine code explains the organism-wide response to sepsis

| PRJNA929971 | ENA