scholarly journals Dynamic changes in human single cell transcriptional signatures during fatal sepsis

2021 ◽  
Author(s):  
Xinru Qiu ◽  
Jiang Li ◽  
Jeff Bonenfant ◽  
Lukasz Jaroszewski ◽  
Walter Klein ◽  
...  
Keyword(s):  
Single Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Metabolic Pathways ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Peripheral Blood Mononuclear ◽  
Repeated Measures Design ◽  
Blood Mononuclear Cells ◽  
Fatal Sepsis

AbstractSystemic infections, especially in patients with chronic diseases, result in sepsis: an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Sepsis survivors and non-survivors oftentimes have similar clinical phenotypes or sepsis biomarker expression upon diagnosis, suggesting that the dynamics of sepsis in the critical early stage may have an impact on these opposite outcomes. To investigate this, we designed a within-subject study of patients with systemic gram-negative bacterial sepsis with surviving and fatal outcomes and performed single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis recognition and 6 hours. We observed that the largest sepsis-induced expression changes over time in surviving versus fatal sepsis were in CD14+ monocytes, including gene signatures previously reported for sepsis outcomes. We further identify changes in the metabolic pathways of both monocytes and platelets, the emergence of erythroid precursors, and T cell exhaustion signatures, with the most extreme differences occurring between the non-sepsis control and the sepsis non-survivor. Our single-cell observations are consistent with trends from public datasets but also reveal specific effects in individual immune cell populations, which change within hours. In conclusion, this pilot study provides the first single-cell results with a repeated measures design in sepsis to analyze the temporal changes in the immune cell population behavior in surviving or fatal sepsis. These findings indicate that tracking temporal expression changes in specific cell-types could lead to more accurate predictions of sepsis outcomes. We also identify molecular pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.Summary sentenceSingle cell transcriptomics of peripheral blood mononuclear cells in surviving and fatal sepsis reveal inflammatory and metabolic pathways that change within hours of sepsis recognition.

scholarly journals Gene-regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells

2021 ◽  
Author(s):  
Cantong Zhang ◽  
Xiaoping Hong ◽  
Haiyan Yu ◽  
Hongwei Wu ◽  
Huixuan Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
High Resolution Map ◽  
The Impact ◽  
Accessible Chromatin

Abstract Rheumatoid arthritis is a chronic autoinflammatory disease with an elusive etiology. Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. However, the impact of epigenetic technology on autoimmune diseases has not been objectively analyzed. Therefore, scATAC-seq was performed to generate a high-resolution map of accessible loci in peripheral blood mononuclear cells (PBMCs) of RA patients at the single-cell level. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of RA at single-cell resolution. In our research, we obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in the RA pathogenesis by regulating the activity of MAP kinase. Consequently, two genes (PTPRC, SPAG9) regulated by 10 key TFs were found that may be associated with RA disease pathogenesis and these TFs were obviously enriched in RA patients (p<0.05, FC>1.2). With further qPCR validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs (ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), MEF2B). What is more, the eight TFs showed highly accessible binding sites in RA patients. These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived PBMCs, providing insights on therapy from an epigenetic perspective.

scholarly journals MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis

2019 ◽  
Author(s):  
Tao Huang ◽  
Jun Zhang ◽  
Wujian Ke ◽  
Xiaohui Zhang ◽  
Wentao Chen ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Treponema Pallidum ◽  
Target Sequence ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Background Treponema pallidum ( T. pallidum ) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum . Methods In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis. Results A total of 89 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states ( P <0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals. Conclusions This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.

scholarly journals IMMU-20. SINGLE CELL CYTOMICS OF PERIPHERAL BLOOD MONONUCLEAR CELLS REVEALS NEW AVENUES FOR GLIOMA IMMUNOTHERAPY

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi125-vi125
Author(s):  
Sophie Dusoswa ◽  
Jan Verhoeff ◽  
Matheus Crommentuijn ◽  
Tom Würdinger ◽  
David Noske ◽  
...  
Keyword(s):  
Single Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Immune dysregulation in peripheral blood mononuclear cells from patients with liver cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 55-55
Author(s):  
Juhua Zhou
Keyword(s):  
Liver Cancer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Critical Role ◽  
Immune Dysregulation ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Underlying Mechanisms

55 Background: Immune regulation may play an important role in cancer development. The immune dysregulation and underlying mechanisms in patients with liver cancer have not fully understood. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from patients with liver cancer. Deep-sequencing, FACS analysis, ELISA and real-time PCR were used to analyze the immune dysregulation and underlying mechanisms in patients with liver cancer. Results: Our analysis discovered that the percentages of immune cell populations in PBMC from patients with liver cancer were significantly different from those in normal controls. Specifically, the percents of B cells and regulatory T cells were high in PBMC from patients with liver cancer. Expression of 161 genes such as EGF, IRF3, CD177, MAP2K2 and MMP9 was found to be significantly inhibited, but 66 genes including CD19, CD70, FOXP1 and IL-32 were significantly up-regulated in PBMC from patients with liver cancer. Further analysis showed that 190 long non-coding RNAs (lncRNAs) were significantly down-regulated; whereas150 lncRNAs were significantly up-regulated in PBMC from patients with liver cancer. Dysregulated lncRNAs were involved in the control of immune cell signaling, cell division and differentiation. Conclusions: The results suggest that the immune dysregulation may play a critical role in the pathogenesis of liver cancer. It also has a great implication in the development of immune therapeutic methods for patients with liver cancer.

In vitro cytokine synthesis in unstimulated and mitogen-stimulated peripheral blood mononuclear cells from individuals with schizophrenia

2019 ◽  
Vol 67 (7) ◽  
pp. 1053-1060
Author(s):  
Elżbieta Kozłowska ◽  
Paulina Żelechowska ◽  
Adam Wysokiński ◽  
Paweł Rasmus ◽  
Anna Łucka ◽  
...  
Keyword(s):  
Immune System ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Peripheral Blood Mononuclear ◽  
Spontaneous Production ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Increasing evidence has shown that the immune system is involved in the schizophrenia development, with alterations in immune cell reactivity being one possible factor contributing to its pathogenesis. The purpose of the study was to evaluate in vitro the capability of peripheral blood mononuclear cells (PBMCs) obtained from subjects with schizophrenia and controls to engage in spontaneous and phytohemagglutinin (PHA)-stimulated cytokine production. The concentrations of various cytokines (interleukin (IL)-1β, IL-17A, tumor necrosis factor (TNF), interferon (IFN)-γ and IL-10) in supernatants from cultured PBMCs were measured using the cytometric bead array. No significant differences in the spontaneous production of IL-1β, IL-17A, IFN-γ and IL-10 by PBMCs were detected between individuals with schizophrenia and controls. TNF synthesis by PBMCs was found to be lower among those with schizophrenia. In all subjects and controls, greater cytokine generation was associated with PBMCs treated with PHA compared with those that were not. The PBMCs from people with schizophrenia displayed considerably higher sensitivity to mitogen stimulation, as the production of IL-17A, TNF and IFN-γ was at least threefold of that observed in healthy subjects, which may be driven by antipsychotics taken by patients with schizophrenia. Correlation was observed between spontaneous production of IFN-γ and Positive and Negative Syndrome Scale G subscore (which measures the general symptoms of schizophrenia) and between PHA-stimulated synthesis of IL–17A and G subscore. Our data confirm that the immune system dysregulation may underlie schizophrenia pathophysiology. There is a potential possibility that immunological tests could be used as a diagnostic, therapeutic and side-effects biomarker for schizophrenia, but further studies are needed.

scholarly journals Invasion of Bovine Peripheral Blood Mononuclear Cells and Erythrocytes by Mycoplasma bovis

2010 ◽  
Vol 78 (11) ◽  
pp. 4570-4578 ◽  
Author(s):  
Jacques van der Merwe ◽  
Tracy Prysliak ◽  
Jose Perez-Casal
Keyword(s):  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Mycoplasma Bovis ◽  
Immune Cell Population ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

ABSTRACT Mycoplasma bovis is a small, cell wall-less bacterium that contributes to a number of chronic inflammatory diseases in both dairy and feedlot cattle, including mastitis and bronchopneumonia. Numerous reports have implicated M. bovis in the activation of the immune system, while at the same time inhibiting immune cell proliferation. However, it is unknown whether the specific immune-cell population M. bovis is capable of attaching to and potentially invading. Here, we demonstrate that incubation of M. bovis Mb1 with bovine peripheral blood mononuclear cells (PBMC) resulted in a significant reduction in their proliferative responses while still remaining viable and capable of gamma interferon secretion. Furthermore, we show that M. bovis Mb1 can be found intracellularly (suggesting a role for either phagocytosis or attachment/invasion) in a number of select bovine PBMC populations (T cells, B cells, monocytes, γδ T cells, dendritic cells, NK cells, cytotoxic T cells, and T-helper cells), as well as red blood cells, albeit it at a significantly lower proportion. M. bovis Mb1 appeared to display three main patterns of intracellular staining: diffuse staining, an association with the intracellular side of the cell membrane, and punctate/vacuole-like staining. The invasion of circulating immune cells and erythrocytes could play an important role in disease pathogenesis by aiding the transport of M. bovis from the lungs to other sites.

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