Interleukin-27-Producing Cells in Gram-negative Neonatal Sepsis Display Diverse Phenotypes and Functions in the Liver
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PROVIDER: PRJNA1195900 | ENA |
REPOSITORIES: ENA
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Project description:Neonates have increased vulnerability to life-threatening infections due to the distinct immune landscape. Interleukin (IL)-27 is a key component of this immune profile that we have previously shown to be elevated in both newborn humans and mice. IL-27 continues to increase in the serum and tissues consistent with poor outcomes during gram-negative neonatal bacterial sepsis. Presently, we dissected the IL-27 producer profile at a single-cell level using IL 27p28eGFP reporter mice in our previously established model of sepsis with luciferase-expressing Escherichia coli. Whole animal imaging regionally highlighted the spleen, liver, and lungs as key infection sites by bacterial luminescence. Flow cytometry showed that IL-27 producers increased in the liver with infection and were predominantly F4/80+ and CD11b+. This information paired with single-cell RNA sequencing further identified the most robust populations as monocytes and derived cells, neutrophils, and Kupffer cells. The transcriptome demonstrated that some populations increased in bactericidal, metabolic, and inflammatory activities while others became less active. Sepsis is a disease characterized by extreme immune dysregulation similar to that shown in our cells. The phenotype and transcriptome of IL-27 producers from the livers of infected animals suggests suppressive activity, which contributes to the dysregulated immune environment observed in sepsis. Together, this work provides previously undescribed insight into the details of IL-27 producers during systemic early life infection. This further provides essential information to support IL-27 as a therapeutic target for neonatal bacterial sepsis.
2025-05-20 | GSE283847 | GEO
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. Keywords: disease state analysis, gram-positive sepsis, gram-negative sepsis
2007-12-01 | GSE6535 | GEO
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. The study included seventy-two critically ill patients admitted to the intensive care unit (ICU) of Nepean Hospital, Sydney, Australia. Of these, fifty-five patients were diagnosed to have sepsis, as confirmed by microbiological culture. The remaining seventeen patients did not have sepsis and were therefore used as controls. The study was approved by the hospital ethics committee and informed consent was obtained from all patients or their relatives. Patient Samples. Whole blood was taken from each patient on admission to ICU. Neutrophils were separated from whole blood using density-gradient separation with Ficoll-PaqueP P(Amersham). Subsequent neutrophil RNA extraction was performed using guanidinium thiocyanate (Ambion). Microarray Experiment. The neutrophil RNA was converted to cDNA, fluorescently labeled and hybridized to its complimentary sequences on the microarray (Invitrogen). The fluorescent signals on each micrroarray were captured using the GenePix 4000B laser scanner (Axon Instruments). Expression level of each gene was represented by the intensity of its fluorescent signal. Data Extraction. All signal intensity values were processed using background-subtraction method. Prior to analysis, all values were log-transformed and normalized by fitting a print-tip group Lowess curve. Normalization minimizes bias due to dye chemistry, signal intensity or location of a gene on the array. It ensures the detection of genes that are truly differentially expressed, instead of those caused by experimental artifacts or variation in the hybridization process. After normalization, genes that had more than 50% of data missing were removed. We then selected genes that had at least 80% of the data showing two-fold changes from the geneâs median values. After filtering, 1617 genes were available for further analysis.
2010-05-25 | E-GEOD-6535 | biostudies-arrayexpress
Project description:The aim of the project is to identify the host response related to Gram positive (S. pyogenes) or Gram negative (E. coli) induced sepsis in a controlled sepsis model. Therefore a well defined baboon sepsis model, established at the Ludwig Boltzmann Institute for experimental and clinical traumatology of Vienna, is used. The overall goal of the project is to define differentially expressed or processed genes which give rise to diagnostic and therapeutic targets and consequently better monitoring and earlier onset of therapy.
2010-04-27 | E-MARS-14 | biostudies-arrayexpress
Project description:The aim of the project is to identify the late (24h) host response related to Gram positive (S. pyogenes) or Gram negative (E. coli) induced sepsis in a controlled sepsis model 24 hours a. Therefore a well defined baboon sepsis model, established at the Ludwig Boltzmann Institute for experimental and clinical traumatology of Vienna, is used. The overall goal of the project is to define differentially expressed or processed genes which give rise to diagnostic and therapeutic targets and consequently better monitoring and earlier onset of therapy.
2010-04-27 | E-MARS-15 | biostudies-arrayexpress
Project description:Carbapenemase_ESBL-producing-Gram-negative_WWTPs
| PRJNA1026089 | ENA
Project description:To identify signature genes that help distinguish (1) sepsis from non-infectious causes of systemic inflammatory response syndrome, (2) between Gram-positive and Gram-negative sepsis. Keywords: Class prediction study
2009-04-01 | GSE9960 | GEO
Project description:To identify signature genes that help distinguish (1) sepsis from non-infectious causes of systemic inflammatory response syndrome, (2) between Gram-positive and Gram-negative sepsis. Experiment Overall Design: A total of 70 critically ill patients (46 sepsis and 24 control) were enrolled in a single-centre observational study. Gene-expression profiling was performed using Affymetrix microarray (U133plus2) with 54,675 transcript. Data was divided into a training set (n=35) and a validation set (n=35). A molecular signature was developed in the training set and was then validated in the validation set.
2009-04-12 | E-GEOD-9960 | biostudies-arrayexpress
Project description:Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. While most information on these cells comes from in vitro studies in humans or in vivo studies in mice, little is known about monocytes under human disease conditions. We investigated the role of monocytes during sepsis and its resolution in humans. A transcriptomal and functional analysis of blood monocytes from patients during gram negative sepsis and at recovery was performed. Monocytes from sepsis patients showed upregulation of a large number of pro-inflammatory genes and cytokines/chemokines, consistent with an ongoing systemic inflammation. However, these cells showed impairment to ex vivo endotoxin (LPS) challenge, displaying a quantitative decrease in the number of LPS-inducible genes. Moreover, they downregulated the expression of several pro-inflammatory cytokine/chemokine genes, activation marker genes and transcription factors associated with monocyte/macrophage activation, upon ex vivo LPS stimulation. Functionally, they downregulated expression of inflammatory cytokines/chemokines and antigen presentation-related molecules and functions. In contrast, genes and functions related to phagocytosis, anti-microbial activity and tissue remodeling where remained unaffected or even enhanced . Collectively, our observations suggest a genetic and functional re-programming of these cells during human sepsis progression. Understanding the molecular mechanisms which regulate this re-programming will allow to devise strategies which could modulate the response of these cells and hence, disease progression. Blood monocytes from gram-negative sepsis patients during sepsis (Sepsis) and following their recovery (Recovery/Basal) as well as healthy donor (control) were isolated. Thereafter, these cells were treated ex vivo with or without LPS for 3h and analysed for transcriptomic study.
2014-05-14 | E-GEOD-46955 | biostudies-arrayexpress
Project description:Interleukin-27-dependent transcriptome signatures regulation of the transcriptome during neonatal sepsis
| PRJNA908112 | ENA