scholarly journals HERV-K Modulates the Immune Response in ALS Patients

2021 ◽  
Vol 9 (8) ◽  
pp. 1784
Author(s):  
Giannina Arru ◽  
Grazia Galleri ◽  
Giovanni A. Deiana ◽  
Ignazio R. Zarbo ◽  
Elia Sechi ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Mononuclear Cells ◽  
Human Endogenous Retrovirus ◽  
Antigenic Peptides ◽  
Proinflammatory Response ◽  
Peripheral Blood Mononuclear ◽  
Great Production ◽  
Als Patients ◽  
Env Glycoprotein

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.

Modified Vaccinia Ankara Virus (MVA) Induces a Th1-Polarized Immune Response in Antigen-Presenting Cells (APCs).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4650-4650
Author(s):  
Christin Flechsig ◽  
Yasemin Suezer ◽  
Markus Kapp ◽  
Gerd Sutter ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Fluorescent Protein ◽  
Conflicts Of Interest ◽  
Human Peripheral Blood ◽  
Cell Transplant ◽  
Peripheral Blood Mononuclear ◽  
Leukocyte Populations

Abstract Abstract 4650 Introduction MVA is one of the most promising vaccine candidates for infectious diseases as well as for malignancies. Astonishingly, little information exists about the mechanism by which immune responses to MVA are generated. It was shown that among leukocytes - which are essential for the generation of cellular and humoral immune responses - APCs like dendritic cells, monocytes and B cells are preferentially infected. But little is known about the effects on APCs. Therefore we wanted to analyze in more detail the general effects of MVA infections on different immune cells. Methods Primary human peripheral blood mononuclear cells (PBMCs) and isolated leukocyte populations in particular monocyte derived DCs, monocytes and B cells were infected with (wildtype) wtMVA or MVA-gfp (green fluorescent protein) to verify the infection. Subsequently changes in surface markers and cytokine expression were assessed. Results Among PBMCs and specific isolated leukocyte populations, monocytes, DCs and B cells were most susceptible to MVA infection. NK cells showed a lower and T cells a very low infection rate. Surprisingly, selected monocytes were less susceptible to MVA as compared to unselected ones. This phenomenon is due to phagocytosis of other infected PBMCs by monocytes. Furthermore we could show that MVA causes a downregulation of CD14 on iDCs and monocytes as well as of CD25, CD80, and CD86 on B cells. Furthermore, there was a slight downregulation of CD1a on iDCs and mDCs and of CD80 on iDCs. On the other hand MVA caused an upregulation of HLA-DR on monocytes and additionally a slight upregulation of CD40 on iDCs. Moreover, MVA evoked a slight upregulation of CD83 on iDCs but a slight downregulation on mDCs. Above all, we could demonstrate that MVA induces an upregulation of CXCL10 in iDCs, mDCs, monocytes, and B cells, and an upregulation of TNFα, IL-6, and IL-12p70 in iDCs, mDCs, and monocytes. In addition, we revealed a downregulation of CXCL8 in monocytes as well as of IL-β in B cells. Conclusions These results suggest that MVA induces a Th1-polarized immune response in APCs. Thus, MVA seems to be an appropriate vaccine vector for antiviral immunotherapy of stem cell transplant recipients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 656 ◽  
Author(s):  
Alba Martín-Moreno ◽  
José L. Jiménez Blanco ◽  
Jamie Mosher ◽  
Douglas R. Swanson ◽  
José M. García Fernández ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Therapeutic Vaccine ◽  
Peptide Delivery ◽  
Antigenic Peptide ◽  
Hydroxyl Groups ◽  
Antigenic Peptides ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

scholarly journals OP0186 CHANGES IN CIRCULATING B CELL LEVELS AND IMMUNOPHENOTYPE ARE ASSOCIATED WITH DEVELOPMENT OF ARTHRITIS FOLLOWING TREATMENT WITH CHECKPOINT INHIBITORS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 112.2-113
Author(s):  
M. Gatto ◽  
S. Bjursten ◽  
C. Jonell ◽  
C. Jonsson ◽  
S. Mcgrath ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cells ◽  
Adverse Events ◽  
B Cell ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Therapy Monitoring ◽  
Cell Subset ◽  
Peripheral Blood Mononuclear ◽  
Transitional B Cells

Background:Inflammatory arthritis (IA) is frequent among rheumatic side effects induced by checkpoint inhibitor (CPI) therapy for metastatic malignancies1. While T cells are likely to sustain the inflammatory process2, fewer data are available concerning the role of B cells3.Objectives:To investigate the phenotype of circulating B cells in patients who develop CPI-induced IA (CPI-IA) and to compare it with features of B cells in patients not developing immune-related adverse events (irAE) upon CPI treatment.Methods:B cell subsets at baseline (before CPI initiation) and during CPI treatment were analyzed in CPI-IA patients and in patients receiving CPI but who did not develop irAE (non-irAE). Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry and B cells were identified as CD19+ and divided into naïve (CD27-IgD+), memory (CD27+IgD+/-), double negative (CD27-IgD-) and transitional (CD10+CD24+CD38+/hi) B cells. Levels of CD21, an activation marker on transitional B cells, were also analyzed. Non-parametric tests were used for analysis of differences between groups.Results:Six CPI-IA and 7 non-irAE patients matched for age, gender and CPI treatment were included, who had received CPI treatment due to metastatic melanoma. Flow cytometry revealed a significant increase of circulating B cells (p=0.002) (Figure 1A) and especially of transitional B cells in CPI-IA patients vs. non-irAE (median %, range: 7.8 (4.5-11.4) vs. 3.2 (1.6-4.3),p=0.007) (Figure 1B), while no remarkable changes were seen across other subsets. Transitional B cell levels significantly decreased from active to quiescent CPI-IA in all patients (p=0.008). In two CPI-IA patients for whom baseline sampling was available, the increase of transitional levels occurred early after CPI treatment and before CPI-IA onset. Levels of expression of CD21 on transitional B cells were increased in CPI-IA vs. non-irAE (p=0.01).Conclusion:Transitional B cells are expanded in CPI-IA patients and seem to increase early after start of CPI therapy. Monitoring this B cell subset might lead to closer follow-up and earlier diagnosis of CPI-IA.References:[1]Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers 2020;6:38[2]Murray-Brown W, Wilsdon TD, Weedon H, et al. Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy. J Immunother Cancer 2020;8:e000281[3]Das R, Bar N, Ferreira M, et al. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest. 2018;128:715-2Disclosure of Interests:None declared

Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences

2010 ◽  
Vol 41 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Pornrutsami Jintaridth ◽  
Apiwat Mutirangura
Keyword(s):  
Mononuclear Cells ◽  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cellular Functions ◽  
Peripheral Blood Mononuclear ◽  
Global Methylation ◽  
Short Interspersed Elements ◽  
Genome Wide ◽  
Age Dependent

Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but also in cancer cells. Loss of LINE-1 methylation has been characterized in many cancers. Here, we evaluated the methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers between 20 and 88 yr of age. Age was negatively associated with methylation levels of Alu (r = −0.452, P < 10−3) and HERV-K (r = −0.326, P < 10−3) but not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during ages 34–68 yr, and loss of methylation of HERV-K occurred during ages 40–63 yr and again during ages 64–83 yr. Interestingly, methylation of Alu and LINE-1 are directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10−3). Therefore, only some types of IRSs lose methylation at certain ages. Moreover, Alu and HERV-K become hypomethylated differently. Finally, there may be several mechanisms of global methylation. However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process.

scholarly journals LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2282
Author(s):  
Björn Koos ◽  
Eva Lotta Moderegger ◽  
Katharina Rump ◽  
Hartmuth Nowak ◽  
Katrin Willemsen ◽  
...  
Keyword(s):  
Immune Response ◽  
Mitochondrial Dna ◽  
Dna Methyltransferase ◽  
Protein Import ◽  
Mononuclear Cells ◽  
Mitochondrial Protein ◽  
Mitochondrial Fraction ◽  
Protein Abundance ◽  
Peripheral Blood Mononuclear ◽  
Cellular Expression

Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA methylation in a human endotoxin model. Peripheral blood mononuclear cells of 20 healthy individuals were isolated from whole blood and stimulated with lipopolysaccharide (LPS) for 48 h. Subsequently, DNMT1 protein abundance was assessed in whole cells and a mitochondrial fraction. At the same time, methylation levels of mtDNA were quantified, and cytokine expression in the supernatant was measured. Despite increased cellular expression of DNMT1 after LPS stimulation, the degree of mtDNA methylation slightly decreased. Strikingly the mitochondrial protein abundance of DNMT1 was reduced by 50% in line with the lower degree of mtDNA methylation. Although only modest alterations were seen in the degree of mtDNA methylation, these strongly correlated with IL-6 and IL-10 expression. Our data may hint at a protein import problem for DNMT1 into the mitochondria under LPS stimulation and suggest a role of demethylated mtDNA in the regulation of the inflammatory immune response.

scholarly journals Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease

2021 ◽  
Vol 8 (6) ◽  
pp. e1087
Author(s):  
Yohei Yamamoto ◽  
Naoko Matsui ◽  
Akiyuki Uzawa ◽  
Yukiko Ozawa ◽  
Tetsuya Kanai ◽  
...  
Keyword(s):  
B Cells ◽  
Myasthenia Gravis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Young Patients ◽  
B Lymphopoiesis ◽  
Peripheral Blood Mononuclear ◽  
Follicular Helper ◽  
Significant Difference ◽  
Cxcr5 Expression

Background and ObjectivesTo investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact.MethodsThymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated.ResultsThe frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy.DiscussionOur findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.

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