scholarly journals Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jiping Liu ◽  
Junbang Wang ◽  
Jinfang Xu ◽  
Han Xia ◽  
Yue Wang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Biological Assays ◽  
Clinical Conditions ◽  
Interferon Responses

AbstractLarge-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

scholarly journals Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

2021 ◽  
Author(s):  
Zhibin Li ◽  
chengcheng Sun ◽  
Fei Wang ◽  
Xiran Wang ◽  
Jiacheng Zhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Evolutionary Biology ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetic Regulatory Networks ◽  
Peripheral Blood Mononuclear

Background: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods: In this study, we compared the single-cell transcriptomes of 77 957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results: The results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular cross-talks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. Conclusions: This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders

scholarly journals Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program

2019 ◽  
Author(s):  
Tanya T. Karagiannis ◽  
John P. Cleary ◽  
Busra Gok ◽  
Nicholas G. Martin ◽  
Elliot C. Nelson ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Types ◽  
Short Exposure ◽  
Opioid Use ◽  
Peripheral Blood Mononuclear ◽  
Antiviral Gene

AbstractChronic opioid usage not only causes addiction behavior through the central nervous system (CNS), but it also modulates the peripheral immune system. However, whether opioid usage positively or negatively impacts the immune system is still controversial. In order to understand the immune modulatory effect of opioids in a systematic and unbiased way, we performed single cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from opioid-dependent individuals and non-dependent controls. We show that chronic opioid usage evokes widespread suppression of interferon-stimulated genes (ISGs) and antiviral gene program in naive monocytes and upon ex vivo stimulation with the pathogen component lipopolysaccharide (LPS) in multiple innate and adaptive immune cell types. Furthermore, scRNA-seq revealed the same phenomenon with in vitro morphine treatment; after just a short exposure to morphine stimulation, we observed the same suppression of antiviral genes in multiple immune cell types. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program, our body’s defense response to potential infection. Our results suggest that further characterization of the immune modulatory effects of opioid use is critical to ensure the safety of clinical opioid usage.

118 COMPARISON OF TRANSCRIPTOME PROFILES FROM ENDOMETRIAL CARUNCLES AND PERIPHERAL BLOOD MONONUCLEAR CELLS REVEAL COMMON AND TISSUE-SPECIFIC BIOLOGICAL PROCESSES REGULATED AT IMPLANTATION IN SHEEP

2015 ◽  
Vol 27 (1) ◽  
pp. 151 ◽  
Author(s):  
V. Mauffré ◽  
O. Sandra ◽  
C. Giraud-Delville ◽  
C. Urien ◽  
L. Jouneau ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Expression Profiles ◽  
Female Reproductive Tract ◽  
Type I ◽  
Cell Trafficking ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

In mammals, implantation is associated with major changes in gene profiles in the female reproductive tract. Molecular signatures of the endometrium have also been shown to vary according to the ability of the embryo to develop to term. Nevertheless, analysing endometrial gene patterns during implantation is incompatible with the maintenance of pregnancy. Therefore early determination of pregnancy issue requires a noninvasive method. Peripheral blood mononuclear cells (PBMC) could represent such an alternative but their reaction to the presence of an implanting embryo has to be investigated. The aim of this study was to investigate gene expression profiles of endometrial caruncular tissue (CAR) and PBMC collected from pregnant ewes (n = 4) and nonpregnant ewes inseminated with inactivated sperm (n = 4) at Day 15 after oestrus. Differentially expressed genes (DEG) were identified using an ovine custom-designed array derived from the ovine 15K Agilent array (Ruscanu et al. 2013 J. Virol. 87, 9333–9343). Data were normalized by Loess and analysed by a linear model in the Limma R package. P-values were corrected using the Benjamini and Hochberg procedure. Comparing pregnancy versus nonpregnancy led to the identification of 2826 DEG in CAR (P < 0.05) and 396 DEG in PBMC (P < 0.10; 265 DEG common with CAR). Ingenuity Pathway Analysis (IPA; Ingenuity Inc., Mountain View, CA, USA) analysis of the 396 PBMC-related DEG revealed 72 overrepresented biological functions (P < 0.001). Among the 15 most overrepresented functions, 13 were common between CAR and PBMC and were mostly related to the immune system, as “infectious disease”, “cell-to-cell signalling and interaction”, “immunological disease”, “immune cell trafficking and inflammatory response”. Using the downstream effect analysis (DEA) of IPA, we identified 163 functions predicted to be increased and 8 functions predicted to be decreased for the CAR DEG dataset, whereas 12 functions were predicted to be increased and 40 functions predicted to be decreased for the PBMC DEG dataset. Interferon (IFN) signalling was strongly present in both datasets, with 44% of PBMC DEG and 29% of CAR DEG found to be related to IFN type I response according to the Interferome database (www.interferome.org). A selection of 12 DEG was validated by qRT-PCR in CAR, intercaruncular areas, and PBMC using 8 pregnant and various groups of nonpregnant ewes (n = 7–9/group). Our data show that PBMC transcriptome is influenced by early pregnancy in sheep, including a major impact of IFN type I such as IFN tau, the signal of maternal recognition of pregnancy. Identifying relevant circulating biomarkers reflecting the quality of the embryo will require further investigation. The authors thank UCEA team (INRA), B. Jost (IGBMC) and F. Moreews (Sigenae).

scholarly journals Hemoglobin drives inflammation and initiates antigen spread and nephritis in lupus

2020 ◽  
Author(s):  
Hritika Sharma ◽  
Anjali Bose ◽  
Uma Kumar ◽  
Rahul Pal
Keyword(s):  
T Cells ◽  
B Cells ◽  
Inflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Autoantibody Production

AbstractHemoglobin (Hb) has well-documented inflammatory effects and is normally efficiently scavenged; clearance mechanisms can be overwhelmed during conditions of erythrocyte lysis, a condition that may occur in systemic lupus erythematosus. Whether Hb is preferentially inflammatory in lupus and additionally induces autoreactivity against prominent autoantigens was assessed. Peripheral blood mononuclear cells derived from SLE patients secreted higher levels of lupus-associated inflammatory cytokines when incubated with Hb, effects negated by haptoglobin. Hb (more particularly, ferric Hb) triggered the preferential release of lupus-associated cytokines from splenocytes, B cells, CD4 T cells, CD8 T cells and plasmacytoid dendritic cells isolated from aging NZM2410 mice, and also had mitogenic effects on B cells. Ferric Hb activated multiple signaling pathways which were differentially responsible for the generation of specific cytokines; inflammatory signaling also appeared to be cell-context dependent. Pull-downs, followed by mass spectrometry, revealed interactions of Hb with several lupus-associated autoantigens; co-incubation of ferric Hb with apoptotic blebs (structures which contain packaged autoantigens, believed to trigger lupus autoreactivity) revealed synergies (in terms of cytokine release and autoantibody production in vitro) that were also restricted to the lupus genotype. Infusion of ferric Hb into NZM2410 mice led to enhanced release of lupus-associated cytokines, the generation of a spectrum of autoantibodies, and enhanced-onset glomerulosclerosis. Given that the biased recognition of ferric Hb in a lupus milieu, in concert with lupus-associated autoantigens, elicits the generation of inflammatory cytokines from multiple immune cell types and stimulates the generation of potentially pathogenic autoantibodies, neutralization of Hb could have beneficial effects.

scholarly journals Fractional response analysis reveals logarithmic cytokine responses in cellular populations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karol Nienałtowski ◽  
Rachel E. Rigby ◽  
Jarosław Walczak ◽  
Karolina E. Zakrzewska ◽  
Edyta Głów ◽  
...  
Keyword(s):  
Single Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Response Analysis ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Fractional Response ◽  
Different Cell Types ◽  
Cell Data

AbstractAlthough we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose–response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, quantifies otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that heterogeneous cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.

Persistent neutralizing antibodies abolish the interferon β bioavailability in MS patients

Neurology ◽  
2003 ◽  
Vol 60 (4) ◽  
pp. 634-639 ◽  
Author(s):  
A. Bertolotto ◽  
F. Gilli ◽  
A. Sala ◽  
M. Capobianco ◽  
S. Malucchi ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Positive Sample ◽  
Type I Interferons ◽  
Type I ◽  
Mrna Levels ◽  
Antiviral Protein ◽  
Peripheral Blood Mononuclear ◽  
Treatment Naïve

Background: MxA is an antiviral protein exclusively induced by type I interferons (IFN) and some viruses, and MxA gene expression is one of the most appropriate markers for measuring the biologic activity of exogenous IFNβ.Methods: A new quantitative-competitive PCR method was used to quantify MxA mRNA in peripheral blood mononuclear cells of 99 treatment-naïve and 92 IFNβ-treated patients with MS (22 Avonex, 17 Betaferon, and 53 Rebif-22). Every 3 months, IFNβ-induced neutralizing antibodies (NAb) were evaluated in sera using a cytopathic effect assay. Three categories of patients were identified: NAb negative (NAb−), persistent NAb positive (NAb+, ≥2 consecutive positive samples), and isolated NAb+ (one positive sample).Results: Treatment-naïve patients expressed detectable MxA mRNA levels (mean = 36 ± 32 fg MxA/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH); range 1 to 160) and an upper normal threshold was established (mean + 3 SD = 132 fg MxA/pg GAPDH). IFNβ-treated patients exhibited more than 11-fold higher levels (mean = 412 ± 282 fg MxA/pg GAPDH; range 16 to 1,172). However, 17 patients did not exhibit an increase in MxA mRNA level; 15 of these 17 patients showed a concurrent Nab+ titer. Moreover, 13 were persistent NAb+. Isolated NAb+ patients did not show a decrease in bioavailability of IFNβ (n = 9; mean = 567 ± 366 fg MxA/pg GAPDH; range 83 to 1,120). In NAb− patients, bioavailability was comparable among the three different IFNβ preparations 12 hours after injection.Conclusion: During IFNβ therapy, the presence of NAb reduced or abolished bioavailability in a relevant percentage of patients. These data could be important for the early detection of patients with MS who are not responsive to IFNβ therapy.

scholarly journals Fractional response analysis reveals logarithmic cytokine responses in cellular populations

2020 ◽  
Author(s):  
Karol Nienałtowski ◽  
Rachel E. Rigby ◽  
Jarosław Walczak ◽  
Karolina E. Zakrzewska ◽  
Jan Rehwinkel ◽  
...  
Keyword(s):  
Single Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Response Analysis ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Fractional Response ◽  
Different Cell Types ◽  
Cell Data

ABSTRACTAlthough we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose-response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, uncovers otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.

scholarly journals Approximate distance correlation for selecting highly interrelated genes across datasets

2021 ◽  
Vol 17 (11) ◽  
pp. e1009548
Author(s):  
Qunlun Shen ◽  
Shihua Zhang
Keyword(s):  
Single Cell ◽  
Large Scale ◽  
Target Gene ◽  
Mononuclear Cells ◽  
Statistical Significance ◽  
Cell Lineage ◽  
Cell Types ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Distance Correlation

With the rapid accumulation of biological omics datasets, decoding the underlying relationships of cross-dataset genes becomes an important issue. Previous studies have attempted to identify differentially expressed genes across datasets. However, it is hard for them to detect interrelated ones. Moreover, existing correlation-based algorithms can only measure the relationship between genes within a single dataset or two multi-modal datasets from the same samples. It is still unclear how to quantify the strength of association of the same gene across two biological datasets with different samples. To this end, we propose Approximate Distance Correlation (ADC) to select interrelated genes with statistical significance across two different biological datasets. ADC first obtains the k most correlated genes for each target gene as its approximate observations, and then calculates the distance correlation (DC) for the target gene across two datasets. ADC repeats this process for all genes and then performs the Benjamini-Hochberg adjustment to control the false discovery rate. We demonstrate the effectiveness of ADC with simulation data and four real applications to select highly interrelated genes across two datasets. These four applications including 21 cancer RNA-seq datasets of different tissues; six single-cell RNA-seq (scRNA-seq) datasets of mouse hematopoietic cells across six different cell types along the hematopoietic cell lineage; five scRNA-seq datasets of pancreatic islet cells across five different technologies; coupled single-cell ATAC-seq (scATAC-seq) and scRNA-seq data of peripheral blood mononuclear cells (PBMC). Extensive results demonstrate that ADC is a powerful tool to uncover interrelated genes with strong biological implications and is scalable to large-scale datasets. Moreover, the number of such genes can serve as a metric to measure the similarity between two datasets, which could characterize the relative difference of diverse cell types and technologies.

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