scholarly journals Single-Cell Immunogenomic Approach Identified SARS-CoV-2 Protective Immune Signatures in Asymptomatic Direct Contacts of COVID-19 Cases

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaushik Sen ◽  
Sudeshna Datta ◽  
Arup Ghosh ◽  
Atimukta Jha ◽  
Abdul Ahad ◽  
...  
Keyword(s):  
Single Cell ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Adaptive Immune ◽  
Interleukin 7 ◽  
Inflammatory Protein ◽  
Cytokine Levels ◽  
Virus Exposure ◽  
Macrophage Inflammatory Protein ◽  
Stimulating Factor

The response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely impacted by the level of virus exposure and status of the host immunity. The nature of protection shown by direct asymptomatic contacts of coronavirus disease 2019 (COVID-19)-positive patients is quite intriguing. In this study, we have characterized the antibody titer, SARS-CoV-2 surrogate virus neutralization, cytokine levels, single-cell T-cell receptor (TCR), and B-cell receptor (BCR) profiling in asymptomatic direct contacts, infected cases, and controls. We observed significant increase in antibodies with neutralizing amplitude in asymptomatic contacts along with cytokines such as Eotaxin, granulocyte-colony stimulating factor (G-CSF), interleukin 7 (IL-7), migration inhibitory factor (MIF), and macrophage inflammatory protein-1α (MIP-1α). Upon single-cell RNA (scRNA) sequencing, we explored the dynamics of the adaptive immune response in few representative asymptomatic close contacts and COVID-19-infected patients. We reported direct asymptomatic contacts to have decreased CD4+ naive T cells with concomitant increase in CD4+ memory and CD8+ Temra cells along with expanded clonotypes compared to infected patients. Noticeable proportions of class switched memory B cells were also observed in them. Overall, these findings gave an insight into the nature of protection in asymptomatic contacts.

scholarly journals Effects of hematopoietic growth factors on the survival of primitive stem cells in liquid suspension culture

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 914-920 ◽  
Author(s):  
DM Bodine ◽  
PS Crosier ◽  
SC Clark
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Cell Function ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Liquid Suspension ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein ◽  
Stimulating Factor

We have examined the effects of 10 different growth factors either alone or in combination on colony-forming unit-spleen (CFU-S) and repopulating stem cell survival in vitro. Either interleukin-3 (IL-3), granulocyte-colony-stimulating factor (G-CSF), or IL-4 alone support CFU-S in vitro. The effects of IL-3 or G-CSF could be neutralized by adding antibodies against IL-3 or G-CSF, respectively. However, the effects of IL-4 could be neutralized with antibodies to IL-4 as well as with antibodies to IL-3 and G-CSF. The combinations of IL-3 and IL-6, IL-3 and G-CSF, IL-3 and IL-1 alpha, IL-3 and granulocyte-macrophage CSF (GM-CSF), and IL-4 and IL-6 acted synergistically to increase CFU-S number. Addition of macrophage inflammatory protein-1 alpha (MIP-1 alpha) to IL-3 and IL-6 inhibited the increase in CFU-S number. Repopulating stem cell function was measured in a competitive repopulation assay. Either IL-3 or IL-4 alone could preserve stem cell function in vitro. The combinations of IL-3 and IL-6, and IL-3 and G- CSF increased stem cell function approximately twofold. The combinations of IL-3 + G-CSF + IL-6, and IL-4 and IL-6 (both of which increased CFU-S number fivefold to 10-fold) decreased stem cell function approximately fourfold. These results demonstrate that certain combinations of growth factors can increase CFU-S number at the expense of stem cell function.

scholarly journals Immunopathologic Alterations in Murine Models of Sepsis of Increasing Severity

1999 ◽  
Vol 67 (12) ◽  
pp. 6603-6610 ◽  
Author(s):  
Samuel Ebong ◽  
Douglas Call ◽  
Jean Nemzek ◽  
Gerald Bolgos ◽  
David Newcomb ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
Local Environment ◽  
Murine Models ◽  
Sham Treatment ◽  
Treatment Groups ◽  
Inflammatory Protein ◽  
Cytokine Levels ◽  
Physiologic Parameters ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

ABSTRACT We investigated inflammatory and physiologic parameters in sepsis models of increasing lethality induced by cecal ligation and puncture (CLP). Mice received imipenem for antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of sepsis increased with needle puncture size (lethality with 18-gauge puncture [18G], 100%; 21G, 50%; 25G, 5%; sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe hypothermia along with decreased activities. A direct correlation was also observed between the severity of sepsis and cytokine (interleukin 1β [IL-1β], tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher cytokine levels in the more severe CLP models than in the sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most endotoxin models. Chemokine (KC and macrophage inflammatory protein 2) profiles also correlated with the severity of sepsis. Except for the chemokines, levels of inflammatory mediators were always higher at the site of inflammation (peritoneum) than in the circulation. Our study demonstrated that sepsis of increasing severity induced increased cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality.

scholarly journals A novel single-cell proliferation assay shows that long-term culture- initiating cell (LTC-IC) maintenance over time results from the extensive proliferation of a small fraction of LTC-IC

Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2137-2145 ◽  
Author(s):  
CM Verfaillie ◽  
JS Miller
Keyword(s):  
Single Cell ◽  
Fluorescence Intensity ◽  
Large Fraction ◽  
Conditioned Media ◽  
Proliferation Assay ◽  
Long Term Culture ◽  
Inflammatory Protein ◽  
Hla Dr ◽  
Macrophage Inflammatory Protein

We have previously shown that when adult marrow CD34+/HLA-DR- cells are cultured for 5 or 8 weeks in the presence of stroma-conditioned media with interleukin-3 (IL-3) and macrophage inflammatory protein-1 alpha (MIP-1 alpha), long-term culture-initiating cells (LTC-IC) are maintained but not expanded. However, if the same cultures are evaluated after 2 weeks, we show that LTC-IC expand 5.5- +/- 0.2-fold. Because expansion of LTC-IC is likely the result of a balance between proliferation and loss of LTC-IC, we hypothesized that, although LTC-IC proliferate in these cultures, loss of a fraction of LTC-IC underlies the lack of long-term expansion. To evaluate the fate of LTC-IC (proliferation, conservation, or loss), we performed PKH-26 labeling assays and developed a single LTC-IC proliferation assay. For PKH-26 labeling assays, CD34+/HLA-DR- cells were incubated with the membrane intercallating dye, PKH-26, before culture for 14 days in stroma- noncontact cultures + IL-3 + MIP-1 alpha. Progeny was reselected by fluorescence-activated cell sorting based on their PKH-26 fluorescence intensity. These studies showed that LTC-IC proliferate because 80% of LTC-IC at week 2 had 0.5 to 1 log lower fluorescence intensity than did freshly labeled CD34+/HLA-DR- cells. To further determine the fate of LTC-IC, we also developed a single LTC-IC proliferation assay. A population of CD34+/CD33- cells, highly enriched in LTC-IC, was sorted singly in stroma-conditioned media+IL-3 + MIP-1 alpha. After 5 weeks, the content of each well was divided equally over 8 secondary stroma- containing wells and cultured for 8 weeks to determine the capacity of the single-cell progeny to initiate 1 or more secondary stromal cultures. Progeny of single-sorted cells were able to initiate up to 8 secondary long-term cultures, demonstrating that LTC-IC proliferate in stroma-conditioned media+IL-3 + MIP-1 alpha. However, more than 65% of single-sorted LTC-IC were not conserved because their progeny could no longer initiate secondary long-term cultures. This finding indicates that, although stromal factors and IL-3 + MIP-1 alpha can induce proliferation of LTC-IC, failure to conserve a large fraction of LTC-IC results in lack of long-term expansion.(ABSTRACT TRUNCATED AT 400 WORDS)

An overview on transmission of diseases in special reference to COVID-19 and potential targets to control this pandemic

2020 ◽  
pp. 05-14
Author(s):  
Vibha Yadav ◽  
Mrigendra Rajput ◽  
Diwakar R.P ◽  
Rajesh Kumar
Keyword(s):  
Rna Virus ◽  
Close Contact ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Adaptive Immune ◽  
Host Cell Receptor ◽  
Positive Sense ◽  
Respiratory Droplets

With its initial outbreak in China, the virus was referred as "coronavirus". WHO has named it "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). It has been described as the successor to SARS-CoV-1which is a positive-sense single-stranded RNA virus. The virus spreads mainly between people who are in close contact (less than two metres or six feet) through small droplets produced during coughing, sneezing, or talking. Infected people exhale the contaminated droplets which are then inhaled into the lungs, or settle on other non- infected people's faces his/her mucosae (mouth and nose) or conjunctiva (eyes) get exposed to potentially infective respiratory droplets to cause new infection. It mainly enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2). Research works are in progress to find potential targets to control the pandemic. To control and treat the virus various targets are under study and these targets range from modulating host cell receptor for the virus entry to generate an effective adaptive immune response.

scholarly journals Systemic Inflammation and Tumour-Infiltrating T-Cell Receptor Repertoire Diversity Are Predictive of Clinical Outcome in High-Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 887
Author(s):  
Vito Olschewski ◽  
Hanno M. Witte ◽  
Veronica Bernard ◽  
Konrad Steinestel ◽  
Wolfgang Peter ◽  
...  
Keyword(s):  
B Cell ◽  
Systemic Inflammation ◽  
Cell Lymphoma ◽  
Adaptive Immune Response ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
High Grade ◽  
Adaptive Immune ◽  
Tcr Repertoire ◽  
Repertoire Diversity

High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (double/triple-hit high grade B-cell lymphoma, HGBL-DH/TH) constitutes a provisional entity among B-cell malignancies with an aggressive behavior and dire prognosis. While evidence for the essential prognostic role of the composition of the tumor-microenvironment (TME) in hematologic malignancies is growing, its prognostic impact in HGBL-DH/TH remains unknown. In this study, we outline the adaptive immune response in a cohort of 47 HGBL-DH/TH and 27 triple-negative diffuse large B-cell lymphoma (tnDLBCL) patients in a large-scale, next-generation sequencing (NGS) investigation of the T-cell receptor (TCR) β-chain repertoire and supplement our findings with data on the Glasgow-Prognostic Score (GPS) at diagnosis, as a score-derived measure of systemic inflammation. We supplement these studies with an immunophenotypic investigation of the TME. Our findings demonstrate that the clonal architecture of the TCR repertoire of HGBL-DH/TH differs significantly from tnDLBCL. Moreover, several entity-exclusive clonotypes, suggestive of tumor-neoantigen selection are identified. Additionally, both productive clonality and percentage of maximum frequency clone as measures of TCR repertoire diversity and tumor-directed activity of the adaptive immune system had significant impact on overall survival (OS; productive clonality: p = 0.0273; HR: 2.839; CI: 1.124–7.169; maximum productive frequency: p = 0.0307; HR: 2.167; CI: 1.074–4.370) but not PFS (productive clonality: p = 0.4459; maximum productive frequency: p = 0.5567) in HGBL-DH/TH patients, while GPS was a significant predictor of both OS and PFS (OS: p < 0.0001; PFS: p = 0.0002). Subsequent multivariate analysis revealed GPS and the revised international prognostic index (R-IPI) to be the only prognosticators holding significant impact for OS (GPS: p = 0.038; R-IPI: p = 0.006) and PFS (GPS: p = 0.029; R-IPI: p = 0.006) in HGBL-DH/TH. Through the identification of expanded, recurrent and entity-exclusive TCR-clonotypes we provide indications for a distinct subset of tumor-neoantigenic elements exclusively shared among HGBL-DH/TH. Further, we demonstrate an adverse prognostic role for both systemic inflammation and uniform adaptive immune response.

scholarly journals Macrophage Inflammatory Protein 1α/CCL3 Is Required for Clearance of an Acute Klebsiella pneumoniae Pulmonary Infection

2001 ◽  
Vol 69 (10) ◽  
pp. 6364-6369 ◽  
Author(s):  
Dennis M. Lindell ◽  
Theodore J. Standiford ◽  
Peter Mancuso ◽  
Zachary J. Leshen ◽  
Gary B. Huffnagle
Keyword(s):  
Klebsiella Pneumoniae ◽  
Alveolar Macrophages ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Macrophage Inflammatory Protein

ABSTRACT The objective of these studies was to determine the role of macrophage inflammatory protein 1α/CCL3 in pulmonary host defense during Klebsiella pneumoniae infection. Following intratracheal inoculation, 7-day survival of CCL3−/− mice was less than 10%, compared to 60% for CCL3+/+ mice. Survival of CCR5−/− mice was equivalent to that of controls, indicating that the enhanced susceptibility of CCL3−/− mice to K. pneumoniae is mediated via another CCL3 receptor, presumably CCR1. At day 3, CFU burden in the lungs of CCL3−/− mice was 800-fold higher than in CCL3+/+ mice, demonstrating that CCL3 is critical for control of bacterial growth in the lung. Surprisingly, CCL3−/− mice had no differences in the recruitment of monocytes/macrophages and even showed enhanced neutrophil recruitment at days 1, 2, and 3 postinfection, compared to CCL3+/+ mice. Therefore, the defect in clearance was not due to insufficient recruitment of leukocytes. No significant differences in cytokine levels of monocyte chemoattractant protein 1 (MCP-1), interleukin 12, gamma interferon, or tumor necrosis factor alpha in lung lavages were found between CCL3+/+ and CCL3−/− mice. CCL3−/− alveolar macrophages were found to have significantly lower phagocytic activity toward K. pneumoniae than CCL3+/+alveolar macrophages. These findings demonstrate that CCL3 production is critical for activation of alveolar macrophages to control the pulmonary growth of the gram-negative bacterium K. pneumoniae.

scholarly journals Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Xu ◽  
Jianping Jia
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Immune Repertoire ◽  
Adaptive Immune ◽  
Peripheral Immune Cells

The peripheral immune system is thought to affect the pathology of the central nervous system in Alzheimer’s disease (AD). However, current knowledge is inadequate for understanding the characteristics of peripheral immune cells in AD. This study aimed to explore the molecular basis of peripheral immune cells and the features of adaptive immune repertoire at a single cell level. We profiled 36,849 peripheral blood mononuclear cells from AD patients with amyloid-positive status and normal controls with amyloid-negative status by 5’ single-cell transcriptome and immune repertoire sequencing using the cell ranger standard analysis procedure. We revealed five immune cell subsets: CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes–macrophages cells, and disentangled the characteristic alterations of cell subset proportion and gene expression patterns in AD. Thirty-one cell type-specific key genes, comprising abundant human leukocyte antigen genes, and multiple immune-related pathways were identified by protein–protein interaction network and pathway enrichment analysis. We also found high-frequency amplification clonotypes in T and B cells and decreased diversity in T cells in AD. As clone amplification suggested the activation of an adaptive immune response against specific antigens, we speculated that the peripheral adaptive immune response, especially mediated by T cells, may have a role in the pathogenesis of AD. This finding may also contribute to further research regarding disease mechanism and the development of immune-related biomarkers or therapy.

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