scholarly journals Hepatitis E Virus Mediates Renal Injury via the Interaction between the Immune Cells and Renal Epithelium

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 454
Author(s):  
Mohamed A. El-Mokhtar ◽  
Mohamed Ismail Seddik ◽  
Asmaa Osman ◽  
Sara Adel ◽  
Essam M. Abdel Aziz ◽  
...  
Keyword(s):  
Immune Cells ◽  
Hepatitis E Virus ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Hepatitis E ◽  
Glomerular Diseases ◽  
Renal Disorder ◽  
Renal Epithelium ◽  
Ifn Γ

Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10+/CD13+ primary proximal tubular (PT) epithelial cells, isolated from healthy donors, were infected with HEV. Inflammatory markers and kidney injury markers were assessed in the presence or absence of peripheral blood mononuclear cells (PBMCs) isolated from the same donors. HEV replicated efficiently in the PT cells as shown by the increase in HEV load over time and the expression of capsid Ag. In the absence of PBMCs, HEV was not nephrotoxic, with no direct effect on the transcription of chemokines (Cxcl-9, Cxcl-10, and Cxcl-11) nor the kidney injury markers (kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin 18 (lL-18)). While higher inflammatory responses, upregulation of chemokines and kidney injury markers expression, and signs of nephrotoxicity were recorded in HEV-infected PT cells cocultured with PBMCs. Interestingly, a significantly higher level of IFN-γ was released in the PBMCs-PT coculture compared to PT alone during HEV infection. In conclusion: The crosstalk between immune cells and renal epithelium and the signal axes IFN-γ/chemokines and IL-18 could be the immune-mediated mechanisms of HEV-induced renal disorder.

scholarly journals The Interplay between Host Innate Immunity and Hepatitis E Virus

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 541 ◽  
Author(s):  
Yang Li ◽  
Changbo Qu ◽  
Peifa Yu ◽  
Xumin Ou ◽  
Qiuwei Pan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Hepatitis E Virus ◽  
Inflammatory Responses ◽  
Hepatitis E ◽  
Experimental Models ◽  
Innate Immune ◽  
Host Immune System ◽  
Global Health Issue ◽  
Host Innate Immunity

Hepatitis E virus (HEV) infection represents an emerging global health issue, whereas the clinical outcomes vary dramatically among different populations. The host innate immune system provides a first-line defense against the infection, but dysregulation may partially contribute to severe pathogenesis. A growing body of evidence has indicated the active response of the host innate immunity to HEV infection both in experimental models and in patients. In turn, HEV has developed sophisticated strategies to counteract the host immune system. In this review, we aim to comprehensively decipher the processes of pathogen recognition, interferon, and inflammatory responses, and the involvement of innate immune cells in HEV infection. We further discuss their implications in understanding the pathogenic mechanisms and developing antiviral therapies.

scholarly journals Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 295 ◽  
Author(s):  
Mohamed A. El-Mokhtar ◽  
Essam R. Othman ◽  
Maha Y. Khashbah ◽  
Ali Ismael ◽  
Mohamed AA Ghaliony ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Stromal Cells ◽  
Hepatitis E Virus ◽  
Inflammatory Responses ◽  
Hepatitis E ◽  
Endometrial Stromal Cells ◽  
Extrahepatic Replication ◽  
Efficient Replication ◽  
Over Time

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.

scholarly journals Rehin Mitigates Chronic Kidney Injury by Decreasing the Release of Perforin and IFN-γ from Immune Cells Via Inhibiting the STING/TBK1/IRF3 Pathway Activation

2022 ◽  
Author(s):  
Jingyu Wang ◽  
Xin Huang ◽  
Yong Liao ◽  
Xintian Cai ◽  
Jing Xu ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Cells ◽  
Medicinal Preparation ◽  
Kidney Injury ◽  
Normal Subjects ◽  
Inflammatory Factor ◽  
Mice Model ◽  
Qrt Pcr ◽  
Ifn Γ

Abstract Shenkang suppository (SKS), a Chinese medicinal preparation rich in various natural ingredients, has not been reported in any studies related to fibrosis. Our experiments validated the anti-fibrotic and anti-inflammatory effects of Rhein (Rh), which is a major component of SKS, and explored its potential immune mechanisms. Tissue and serum specimens from chronic kidney disease (CKD) patients and normal subjects were collected in 30 cases each, and the expression differences of perforin and IFN-γ were analyzed by ELISA. Further, the CKD mice model constructed with folic acid (FA) was used to validate these differences by WB and qRT-PCR to explore the potential nephroprotective mechanism of Rh. Besides, in vitro experiments were conducted to identify the release sources of perforin and IFN-γ. ELISA showed that perforin and IFN-γ were upregulated in CKD patients, and this phenomenon was also corroborated in CKD mice. WB and qRT-PCR data showed that Rh reversed perforin and IFN-γ upregulation, inflammatory factor recruitment, and extracellular matrix (ECM) protein upregulation. Results from in vitro experiments demonstrate that the upregulation of perforin and IFN-γ originates from the stress response of CD4+ T lymphocytes (CD4+ cells), CD8+ T lymphocytes (CD8+ cells) and natural killer cells (NK cells), which can be suppressed by Rh. More importantly, the activated STING/TBK1/IRF3 pathway in CKD was also inhibited by Rh. Our data suggest that Rh possesses anti-fibrotic and nephroprotective effects, which mechanistically are associated with decreased release of perforin and IFN-γ from immune cells, which may be achieved by suppressing the STING/TBK1/IRF3 pathway.

scholarly journals Effects of degradable magnesium on paracrine signaling between human umbilical cord perivascular cells and peripheral blood mononuclear cells

2020 ◽  
Vol 8 (21) ◽  
pp. 5969-5983 ◽  
Author(s):  
Qian Wang ◽  
Lei Xu ◽  
Heike Helmholz ◽  
Regine Willumeit-Römer ◽  
Bérengère J. C. Luthringer-Feyerabend
Keyword(s):  
Stem Cells ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Human Mesenchymal Stem Cells ◽  
Human Umbilical Cord ◽  
Paracrine Signaling ◽  
Regenerative Processes ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Human mesenchymal stem cells (MSC) interact with numerous immune cells that can promote regenerative processes and influence inflammatory responses.

Cordycepin is an Immunoregulatory Active Ingredient of Cordyceps sinensis

2008 ◽  
Vol 36 (05) ◽  
pp. 967-980 ◽  
Author(s):  
Xiaoxia Zhou ◽  
Liping Luo ◽  
Waike Dressel ◽  
Gulibahaer Shadier ◽  
Doreen Krumbiegel ◽  
...  
Keyword(s):  
Immune Cells ◽  
Active Ingredient ◽  
Mononuclear Cells ◽  
Binding Activity ◽  
Cordyceps Sinensis ◽  
Chinese Drug ◽  
Dependent Manner ◽  
Tnf Α ◽  
Ifn Γ ◽  
Regulatory Effects

We have reported that cordycepin, an adenosine derivative from the fungus Cordyceps, increased interleukin (IL)-10 expression, decreased IL-2 expression and suppressed T lymphocyte activity. In the present study, we further characterized the regulatory effects of cordycepin on human immune cells. Moreover, a traditional Chinese drug, Cordyceps sinensis (CS) that contains cordycepin, was also investigated. Cytometric Bead Array (CBA) was used to determine the concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α and IFN-γ in culture of peripheral blood mononuclear cells (PBMCs). The results showed that both cordycepin and CS up-regulated IL-10, IL-1β, IL-6, IL-8 and TNF-α; at the same time, they suppressed phytohemagglutinin (PHA)-induced production of IL-2, IL-4, IL-5, IFN-γ and IL-12. As compared to cordycepin, CS displayed its regulatory effects on IL-2 and IL-10 in a similar dose-dependent manner even with higher efficiency. The binding activity of transcription factors in a human monocytic cell line THP-1 was tested by the trans-AM method, and a higher binding activity of SP1 and SP3 was observed in cordycepin or CS treated cells compared to the control. These results led to the opinion that cordycepin and CS pleiotropically affected the actions of immune cells and cytokine network in a similar fashion. Cordycepin could be an important immunoregulatory active ingredient in Cordyceps sinensis. In addition, CS may contain substances which possess synergism with cordycepin, as CS showed a higher efficiency in the production of IL-10 and IL-2 than cordycepin. However, merits of these effects in pharmacology and clinical medicine have yet to be proven and the precise mechanism of these immune regulatory actions should be researched.

scholarly journals Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Wang ◽  
Xueyue Zheng ◽  
Bingnan Liu ◽  
Yaoyao Xia ◽  
Zhongquan Xin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Hypoxia Inducible Factor ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ifn Γ ◽  
Inflammatory Macrophages

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1β (IL-1β) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1α (HIF-1α) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.

Immune Cells in Ischemic Acute Kidney Injury

2019 ◽  
Vol 20 (8) ◽  
pp. 770-776 ◽  
Author(s):  
Long Zheng ◽  
Wenjun Gao ◽  
Chao Hu ◽  
Cheng Yang ◽  
Ruiming Rong
Keyword(s):  
Acute Kidney Injury ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Systemic Disease ◽  
Kidney Injury ◽  
Repair Process ◽  
Injured Kidney

Acute kidney injury (AKI) is a systemic disease characterized by acute loss of renal function and accumulation of end products of nitrogen metabolism. Ischemic AKI is the most common cause of AKI, and inflammatory responses are inevitablely involved in ischemic AKI. In the process of ischemic AKI, multiple factors are involved in activating and recruitment of immune cell to the injured kidney. These factors include DAMPs and HIFs released from the injured kidney, increased expression of adhesion molecules, the production of chemokines and cytokines, activation of complement system and TLRs as well as the permeability dysfunction of the renal vascular endothelium. Immune cells of both the innate and adaptive immune systems, such as neutrophils, dendritic cells, macrophages and lymphocytes contribute to the pathogenesis of renal injury after ischemia reperfusion injury (IRI), with some of their subpopulations also participating in the repair process. Numerous studies of immune cells involved in the pathogenesis of AKI have enhanced the understanding of their possible mechanisms in AKI which might become the potential targets for the treatment of ischemic AKI. This review describes the function of the immune cells in the pathogenesis and repair of ischemic AKI and emphasizes the treatment of ischemic AKI potentially targeting them.

scholarly journals The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE

2018 ◽  
Vol 77 (7) ◽  
pp. 1070-1077 ◽  
Author(s):  
Niklas Hagberg ◽  
Martin Joelsson ◽  
Dag Leonard ◽  
Sarah Reid ◽  
Maija-Leena Eloranta ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Kinase Inhibitors ◽  
Mononuclear Cells ◽  
Risk Allele ◽  
Severe Disease ◽  
Janus Kinase ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ObjectivesGenetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs.ResultsIn resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively.ConclusionsT cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.

scholarly journals Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1950
Author(s):  
Weimin Yang ◽  
Shuangfeng Chen ◽  
Houfack K. Mickael ◽  
Liangheng Xu ◽  
Yueping Xia ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Hepatitis E Virus ◽  
Inflammatory Responses ◽  
Hepatitis E ◽  
Adverse Pregnancy Outcomes ◽  
Vegf Expression ◽  
Genotype 4 ◽  
Infected Female ◽  
Expression Levels ◽  
Adverse Pregnancy

To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.

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