scholarly journals COVID-19 Specific Immune Markers Revealed by Single Cell Phenotypic Profiling

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1794
Author(s):  
Francesca Sansico ◽  
Mattia Miroballo ◽  
Daniele Salvatore Bianco ◽  
Francesco Tamiro ◽  
Mattia Colucci ◽  
...  
Keyword(s):  
Viral Infection ◽  
Single Cell ◽  
Peripheral Blood ◽  
Blood Donors ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Surface Markers ◽  
Immune Functions ◽  
Immune Markers

COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophenotypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the peripheral blood have been well documented. Nonetheless, their effects on COVID-19-related cell heterogeneity and disease progression are less defined. Here, we performed a single-cell RNA sequencing of about 400 transcripts relevant to immune cell function including surface markers, in mononuclear cells (PBMCs) from the peripheral blood of 50 subjects, infected with SARS-CoV-2 at the diagnosis and 27 healthy blood donors as control. We found that patients with COVID-19 exhibited an increase in COVID-specific surface markers in different subsets of immune cell composition. Interestingly, the expression of cell receptors, such as IFNGR1 and CXCR4, was reduced in response to the viral infection and associated with the inhibition of the related signaling pathways and immune functions. These results highlight novel immunoreceptors, selectively expressed in COVID-19 patients, which affect the immune functionality and are correlated with clinical outcomes.

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 Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway.

1981 ◽  
Vol 154 (3) ◽  
pp. 892-906 ◽  
Author(s):  
B S Schwartz ◽  
T S Edgington
Keyword(s):  
Immune Complex ◽  
Immune Complexes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Human Peripheral Blood ◽  
Procoagulant Activity ◽  
Cell Fractionation ◽  
Soluble Immune Complexes

It has previously been described that soluble antigen:antibody complexes in antigen excess can induce an increase in the procoagulant activity of human peripheral blood mononuclear cells. It has been proposed that this response may explain the presence of fibrin in immune complex-mediated tissue lesions. In the present study we define cellular participants and their roles in the procoagulant response to soluble immune complexes. Monocytes were shown by cell fractionation and by a direct cytologic assay to be the cell of origin of the procoagulant activity; and virtually all monocytes were able to participate in the response. Monocytes, however, required the presence of lymphocytes to respond. The procoagulant response required cell cooperation, and this collaborative interaction between lymphocytes and monocytes appeared to be unidirectional. Lymphocytes once triggered by immune complexes induced monocytes to synthesize the procoagulant product. Intact viable lymphocytes were required to present instructions to monocytes; no soluble mediator could be found to subserve this function. Indeed, all that appeared necessary to induce monocytes to produce procoagulant activity was an encounter with lymphocytes that had previously been in contact with soluble immune complexes. The optimum cellular ratio for this interaction was four lymphocytes per monocyte, about half the ratio in peripheral blood. The procoagulant response was rapid, reaching a maximum within 6 h after exposure to antigen:antibody complexes. The procoagulant activity was consistent with tissue factor because Factors VII and X and prothrombin were required for clotting of fibrinogen. WE propose that this pathway differs from a number of others involving cells of the immune system. Elucidation of the pathway may clarify the role of this lymphocyte-instructed monocyte response in the Shwartzman phenomenon and other thrombohemorrhagic events associated with immune cell function and the formation of immune complexes.

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.

Surfactant protein A stimulation of inflammatory cytokine and immunoglobulin production

1994 ◽  
Vol 267 (6) ◽  
pp. L712-L719 ◽  
Author(s):  
S. G. Kremlev ◽  
D. S. Phelps
Keyword(s):  
Interferon Gamma ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Human Peripheral Blood ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Tnf Alpha

Pulmonary surfactant plays a variety of roles related to the regulation of immune function in the lung. Of particular interest in this regard is surfactant protein A (SP-A), a calcium-dependent lectin. We have reported previously that SP-A enhances concanavalin A-induced proliferation, and in this study we examined the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukins 1 alpha, 1 beta, and 6, and interferon-gamma by human peripheral blood mononuclear cells. Levels of all of the cytokines except interferon-gamma were increased by SP-A. In rat peripheral blood cells, splenocytes, and alveolar macrophages we found a similar enhancement of TNF-alpha release by SP-A. In combinations of SP-A and surfactant lipids, the increased levels of TNF-alpha resulting from SP-A treatment decreased as the lipids increased. At higher relative concentrations of SP-A, the lipids had little or no effect. SP-A also enhanced the production of immunoglobulins A, G, and M by rat splenocytes. Levels of each isotype were increased severalfold over control levels. These data demonstrate that SP-A is capable of modulating immune cell function in the lung by regulating cytokine production and immunoglobulin secretion.

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 ◽  
Cell Function ◽  
Immune Cell ◽  
Treponema Pallidum ◽  
Target Sequence ◽  
Peripheral Blood Mononuclear ◽  
Non Invasive ◽  
Significant Difference ◽  
Differentially Expressed Mirnas

Abstract Background Treponema pallidum (T. pallidum Tp) infection evokes vigorous immune responses, resulting in tissue damage. The immune mechanism after Treponema pallidum infection is still not clear. MicroRNAs (miRNAs) have been shown, however, to influence immune cell function and consequently the generation of antibody responses during other microbe infections, but these values are unknown for Tp. Methods In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy persons, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. MiRNAs were profiled from patient peripheral blood obtained at the time of serological diagnosis. Then both the target sequence analysis on these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative RT-PCR for analysis of microRNA Results There were 89 differentially regulated miRNA identified in total. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant difference among serofast state, and serological cure (P<0.05). A miRNAs (hsa-miR-195-5p) showed significant differences among untreated patients and healthy individuals. Conclusions This is the first study of miRNA expression difference in PBMCs in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as non-invasive biomarkers of Treponema pallidum infections, which will facilitate better diagnosis and treat of T. pallium infections.

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 Immune Cell Landscape of Patients With Diabetic Macular Edema by Single-Cell RNA Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Pengjuan Ma ◽  
Ping Zhang ◽  
Shuxia Chen ◽  
Wen Shi ◽  
Jinguo Ye ◽  
...  
Keyword(s):  
Macular Edema ◽  
Single Cell ◽  
Differential Expression ◽  
Signaling Pathway ◽  
Diabetic Macular Edema ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Differential Expression Analysis

Purpose: We performed single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to determine phenotype and function of peripheral immune cells in patients with diabetic macular edema (DME).Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy controls (HC). The single-cell samples were loaded on the Chromium platform (10x Genomics) for sequencing. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization.Results: We constructed a single-cell RNA atlas comprising 57,650 PBMCs (24,919 HC, 32,731 DME). We divided all immune cells into five major immune cell lineages, including monocytes (MC), T cells (TC), NK cells (NK), B cells (BC), and dendritic cells (DC). Our differential expression gene (DEG) analysis showed that MC was enriched of genes participating in the cytokine pathway and inflammation activation. We further subdivided MC into five subsets: resting CD14++ MC, proinflammatory CD14++ MC, intermediate MC, resting CD16++ MC and pro-inflammatory CD16++ MC. Remarkably, we revealed that the proinflammatory CD14++ monocytes predominated in promoting inflammation, mainly by increasingly production of inflammatory cytokines (TNF, IL1B, and NFKBIA) and chemokines (CCL3, CCL3L1, CCL4L2, CXCL2, and CXCL8). Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that the proinflammatory CD14++ monocytes, especially in DME patients, upregulated inflammatory pathways including tumor necrosis factor-mediated signaling pathway, I-kappaB kinase/NF-kappaB signaling, and toll-like receptor signaling pathway.Conclusion: In this study, we construct the first immune landscape of DME patients with T2D and confirmed innate immune dysregulation in peripheral blood based on an unbiased scRNA-seq approach. And these results demonstrate potential target cell population for anti-inflammation treatments.

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

2020 ◽  
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 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 MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis

2020 ◽  
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.

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