Multidimensional and longitudinal immune profiling of sepsis in Uganda
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PROVIDER: PRJNA1220203 | ENA |
REPOSITORIES: ENA
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Project description:Multidimensional and longitudinal immune profiling of sepsis in Uganda
| PRJNA1220204 | ENA
Project description:Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combined multi-parameter flow cytometry, single-cell RNA sequencing (scRNAseq) and targeted plasma analysis to prospectively and longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identified a dynamically changing peripheral blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and monocyte HLA-DR expression, which characterized sepsis even when the common clinical marker of inflammation, C-reactive protein (CRP) was not elevated. Furthermore, scRNAseq showed upregulation of amphiregulin in different leukocyte populations during sepsis, which we validated as a plasma analyte that correlated with clinical signs of disease, even when CRP was normal. This study provides new insights into immune pathways associated with early-life sepsis and identifies potential immune analytes as diagnostic adjuncts for sepsis to guide targeted antibiotic prescribing.
2023-11-23 | GSE236099 | GEO
Project description:Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Although our understanding in the pathophysiological features of sepsis has increased significantly during the past decades, there is still lack of mechanism of sepis.Neutrophils are important regulators against invading pathogens, and their role during sepsis has been studied extensively. However, whether neutrophils could inhibit the immune response of CD8+T cells and the mechanism is unkown in sepsis.
2022-07-06 | GSE186054 | GEO
Project description:Genomic shotgun sequences of Trypanosoma brucei brucei from Uganda with minimal laboratory passage.
2020-11-22 | E-MTAB-9759 | biostudies-arrayexpress
Project description:Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression and emergency hematopoiesis. Epigenetic changes, notably via histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we discovered broad changes in DNA methylation throughout the genome of exhausted monocytes, including at several genes implicated in immune dysregulation during sepsis and Covid-19 infection (e.g. Plac8). Methylome reprogramming is driven in part by Wnt signaling inhibition in exhausted monocytes, and can be reversed with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. These changes are recapitulated in septic mice following cecal slurry injection, supporting the involvement of DNA methylation in acute and long-term monocyte dysregulation during sepsis.
2024-03-05 | GSE242816 | GEO
Project description:Sepsis is the most common cause of hospitalization worldwide. Millions of people survive sepsis each year and are at risk for rehospitalization and death. Pulmonary complications such as respiratory failure due to pneumonia and exacerbation of chronic respiratory disease are among the most common reasons for rehospitalization in sepsis survivors. In order to prevent additional morbidity and death in patients surviving sepsis, we must establish biomarkers to identify patients at risk for pulmonary complications and develop treatments. Late complications in sepsis survivors, particularly nosocomial infections, are proposed to occur through persistent immune reprogramming after sepsis known as immunoparalysis. However, pro-inflammatory immune reprogramming in the form of primed or enhanced responses to secondary stimuli has also been described and could directly contribute to tissue injury and death. Primed immune responses and their contribution to long-term sepsis complications remains understudied. We hypothesize that primed immune responses to inflammatory stimuli in the lung after sepsis are associated with pulmonary complications in survivors of sepsis. To this end, we developed a model of antibiotic treated sepsis induced by cecal ligation and puncture followed three weeks later by secondary challenge with intranasal lipopolysaccharide to induce inflammatory lung injury. We find that mice surviving sepsis have enhanced lung injury responses in the setting of an exaggerated proinflammatory immune response, including primed Ly6Chi monocyte Tnf expression. Using RNA sequencing, we identified derangements in lung gene expression after CLP prior to LPS administration which may mediate enhanced lung injury in this model. One potential mediator, S100A8/A9, was also found to be elevated in the circulation of human sepsis survivors for up to 180 days after sepsis. These findings validate our model and identify S100A8/A9 as one of many potential biomarkers and therapeutic targets for patients at risk for long-term pulmonary complications after sepsis. The role of S100A8/A9, monocyte priming, and other factors predisposing to enhanced lung injury responses and pulmonary complications after sepsis warrant further investigation in humans and mice.
2021-06-23 | GSE168796 | GEO
Project description:Multidimensional Styela plicata microbiome
| PRJEB61940 | ENA
Project description:Background: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality. Results: The Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS) or sepsis (infection with SIRS), including 78 sepsis survivors and 28 sepsis nonsurvivors, who had previously undergone plasma proteomic and metabolomic profiling. The expression of 338 genes differed between subjects with SIRS and those with sepsis, primarily reflective of immune activation in sepsis. The expression of 1,238 genes differed with sepsis outcome: Nonsurvivors had lower expression of many immune function-related genes. Functional genetic variants associated with sepsis mortality were sought based on a common disease â rare variant hypothesis. VPS9D1, whose expression was increased in sepsis survivors, had a higher burden of missense variants in sepsis survivors, and these were associated with altered expression of 3,799 genes, primarily reflecting Golgi and endosome biology. Conclusions: Host response in sepsis survivors â activation of immune response-related genes â was muted in sepsis nonsurvivors. The association of sepsis survival with robust immune response and presence of missense variants in VPS9D1 warrants replication and further functional studies. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS, n=23) or sepsis (infection with SIRS), including 78 sepsis survivors and 28 sepsis nonsurvivors, who had previously undergone plasma proteomic and metabolomic profiling.
2015-01-01 | E-GEOD-63042 | biostudies-arrayexpress
Project description:Anopheles arabiensis from Jinja, Uganda resistant to permethrin (1hr exposure) were compared to sympatric controls and two pyrethroid susceptible colonies of An. arabiensis (Moz and Dongola)
2014-02-01 | E-MTAB-1873 | biostudies-arrayexpress
Project description:The diversity of human immune responses to P. falciparum is unknown and yet immune decision-making likely dictates outcome of infection We infected 15 malaria-naïve human volunteers with P. falciparum and used longitudinal whole blood transcriptional profiling to independently analyse the immune response in every volunteer
2020-09-07 | GSE132050 | GEO