scholarly journals Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 223
Author(s):  
Priscila Conrado Guerra Nunes ◽  
Lilimar da Silveira Rioja ◽  
Janice Mery Chicarino de Oliveira Coelho ◽  
Natália Gedeão Salomão ◽  
Kíssila Rabelo ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Renal Injury ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Severe Disease ◽  
Renal Involvement ◽  
High Viral Load ◽  
Renal Tissue ◽  
Cortical Region

Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host 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 DNA Damage Response and Oxidative Stress in Systemic Autoimmunity

2019 ◽  
Vol 21 (1) ◽  
pp. 55 ◽  
Author(s):  
Vassilis L. Souliotis ◽  
Nikolaos I. Vlachogiannis ◽  
Maria Pappa ◽  
Alexandra Argyriou ◽  
Panagiotis A. Ntouros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Dna Damage ◽  
Autoimmune Diseases ◽  
Dna Damage Response ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Systemic Autoimmune Diseases ◽  
Damage Response

The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.

scholarly journals Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

2020 ◽  
Vol 21 (6) ◽  
pp. 2248 ◽  
Author(s):  
Abu Sufiun ◽  
Asadur Rahman ◽  
Kazi Rafiq ◽  
Yoshihide Fujisawa ◽  
Daisuke Nakano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
The Difference

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

scholarly journals Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)

2020 ◽  
Vol 27 (11) ◽  
pp. 3196-3207 ◽  
Author(s):  
Chiara Agrati ◽  
Alessandra Sacchi ◽  
Veronica Bordoni ◽  
Eleonora Cimini ◽  
Stefania Notari ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Functions ◽  
Convalescent Phase

Abstract SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-β, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-β and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.

Costimulatory effects of IL-12 on HBV-induced immune response are suppressed in patients with a high viral load

1998 ◽  
Vol 114 ◽  
pp. A1336
Author(s):  
J.F. Schlaak ◽  
G. Tully ◽  
H.F. Löhr ◽  
G. Gerken ◽  
K.-H. Meyer zum Büschenfelde
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
High Viral Load

The role of nitric oxide in iron-induced rat renal injury

2004 ◽  
Vol 23 (11) ◽  
pp. 533-536 ◽  
Author(s):  
M Kadkhodaee ◽  
A Gol
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Vitamin E ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
No Synthase ◽  
Plasma Vitamin ◽  
Anti Oxidant ◽  
Plasma Vitamin E

Iron overload and enhanced hydroxyl radical (•OH) formation have been implicated as the causative factors of oxidative stress in different organs. Both pro-oxidant and anti-oxidant properties have been reported for nitric oxide (NO) in iron-mediated tissue injury. To determine the contribution of NO to iron-induced renal injury, eight groups of rats (eight in each group) were studied as follows: control (normal saline), L-Arg (L-arginine as a substrate of NO synthase, 400 mg/kg), L-NAME (an inhibitor of NO synthase, 8 mg/kg), Fe (iron dextran, 600 mg/kg), DFO (deferroxamine as a chelator of iron, 150 mg/kg), Fe+L-Arg, Fe+L-NAME, DFO+L-Arg. Twenty-four hours after the injections, blood samples were taken and kidneys removed for biochemical analysis. Plasma creatinine and urea were used to stimulate renal function. Renal tissue and plasma vitamin E levels, the most important endogenous fat soluble antioxidant, were measured by HPLC and UV detection. In this study, renal function was markedly reduced in the Fe group compared to controls (creatinine, 1.02± 0.05 mg/dL versus 0.78±0.04 P <0.05; urea, 49.59±1.69 mg/dL versus 40.75±0.86, P <0.01). Vitamin E levels were significantly lower in the Fe group compared to controls (plasma P <0.01; renal tissue P <0.05). Administration of L-Arg to Fe-treated groups prevented these reductions. L-NAME increased iron-induced toxicity significantly, demonstrated by further reduction in the vitamin E levels and renal function compared to the Fe group alone. We concluded that NO plays an important role in protecting the kidney from iron-induced nephrotoxicity. NO synthase blockade enhances iron-mediated renal toxicity in this model.

scholarly journals Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ioannis P. Trougakos ◽  
Evangelos Terpos ◽  
Christina Zirou ◽  
Aimilia D. Sklirou ◽  
Filia Apostolakou ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Natural Infection ◽  
Severe Disease ◽  
Vaccination Campaign ◽  
Hospitalized Patients ◽  
Peripheral Blood Mononuclear ◽  
Post Vaccination ◽  
Antibody Titers

Abstract Background Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. Methods Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). Results We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. Conclusions These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection. Graphical abstract

scholarly journals Probiotics in the management of respiratory diseases: ways of interaction and therapeutic perspectives

2019 ◽  
pp. 173-182
Author(s):  
I. N. Zakharova ◽  
I. V. Berezhnaya ◽  
L. Ya. Klimov ◽  
A. N. Kasyanova ◽  
O. V. Dedikova ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Diseases ◽  
Respiratory Infections ◽  
High Viral Load ◽  
Sufficient Detail ◽  
Probiotic Strains

Today, the composition of the gut microbiota has been studied in sufficient detail. Increasing number of studies show that the respiratory tract, both the upper and lower respiratory tract, have their own microbiota. The article presents the main today’s data about the species diversity of microorganisms in the respiratory and gastrointestinal tracts, describes the role of a healthy microbiota in providing local and general immunity. The authors specify the role of probiotic strains of microorganisms and their effect on various parts of the immune response and present the data of studies on the effect of probiotic products on the immunological resistance of humans, especially the respiratory tract with high viral load. Restoration of a healthy microbiota in the human tract using probiotic products administered through the gastrointestinal tract can reduce the risk and severity of manifestation of the respiratory infections.

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