Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells (ATAC-Seq)
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ABSTRACT:
PROVIDER: PRJNA729502 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14513484_1.fastq.gz | Fastqsanger.gz | |||
| SRR14513484_2.fastq.gz | Fastqsanger.gz | |||
| SRR14513485_1.fastq.gz | Fastqsanger.gz | |||
| SRR14513485_2.fastq.gz | Fastqsanger.gz | |||
| SRR14513486_1.fastq.gz | Fastqsanger.gz |
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Project description:Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
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Project description:Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells (RNA-Seq)
| PRJNA729503 | ENA
Project description:Determine genome-wide open chromatin in P14 memory CD8 T cells 30 days after septic insult
2021-10-14 | GSE174358 | GEO
Project description:Determine genome-wide open chromatin in P14 memory CD8 T cells 30 days after septic insult
2021-10-14 | GSE174357 | GEO
Project description:The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (TCM) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that TCM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection.
| S-EPMC8589447 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-14 | GSE174359 | GEO
Project description:Our experiments examined T-lymphocyte numbers and effector-functions in peritoneal contamination and infection (PCI) a mouse model of sepsis. One of our main questions was how T-lymphocytes reconstitute after sepsis-induced lymphopenia. We investigated the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Sepsis is an immunological dysfunction against pathogens leading to inflammation with massive cytokine production. Simultaneously immunosuppression occurs e.g. lymphopenia, which is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. More than 50% of T-cells undergo apoptosis shortly after sepsis-induction. However, 8 days after sepsis onset, surviving mice present normal lymphocyte counts. Theoretically, T-cells could reconstitute in two different ways. Firstly, the diminished pool of T-cells is replenished by newly in thymus produced T-cells with new diverse T-cell-receptors (TCRs). Alternatively, remaining T-cells start to proliferate until reaching normal cell count. If this was the case all divided cells shared the same TCRs as primary cells. This could lead to a narrowed TCR diversity within a quantitative normalized T-cell pool and would be an explanation for the long-lasting immune incompetence. To address the question how T-cells recover from lymphopenia we applied next generation sequencing (NGS) to analyse TCR diversity in septic and healthy mice. One group of septic mice received Interleukin-7 (IL-7), an interleukin which regulates T-cell homeostasis and is a promising therapeutically approach for septic patients. 50000 sequences per mouse were analyzed and the three different groups (controls, sepsis, sepsis + IL-7 treatment) compared regarding their diversity. The sequenced raw data (fastq) are uploaded in this library.
2019-10-02 | E-MTAB-7483 | 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, an amplified immune response to systemic infection, is characterized by a transient cytokine storm followed by chronic immune dysfunction. Consequently, sepsis survivors are highly susceptible to newly introduced infections, suggesting sepsis can influence the function and composition of the naïve CD8 T cell pool and resulting pathogen-induced primary CD8 T cell responses. Here, we explored the extent to which sepsis induces phenotypic and functional changes within the naïve CD8 T cell pool. To interrogate this, the cecal ligation and puncture (CLP) mouse model of polymicrobial sepsis was used. In normal, non-septic mice, we show type-I interferon (IFN I)-mediated signaling plays an important role in driving the phenotypic and functional heterogeneity in the naïve CD8 T cell compartment leading to increased representation of Ly6C+ naïve CD8 T cells. In response to viral infection after sepsis resolution, naïve Ly6C+ CD8 T cells generated more primary effector and memory CD8 T cells with slower conversion to a central memory CD8 T cell phenotype (Tcm) than Ly6C- naïve CD8 T cells. Importantly, as a potent inducer of cytokine storm and IFN I production, sepsis leads to increased representation of Ly6C+ naïve CD8 T cells that maintained their heightened ability to respond (i.e., effector and memory CD8 T cell accumulation and cytokine production) to primary LCMV infection. Lastly, longitudinal analyses of peripheral blood samples obtained from septic patients revealed profound changes in CD8 T cell subset composition and frequency compared to healthy controls. Thus, sepsis has the capacity to alter the composition of naïve CD8 T cells, directly influencing primary CD8 T cell responses to newly introduced infections.
| S-EPMC10597476 | biostudies-literature
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 | GSE253201 | GEO