scholarly journals Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christian Rodriguez Rodrigues ◽  
María Celeste Nicolao ◽  
Maia Chop ◽  
Natalia Plá ◽  
Mora Massaro ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Innate Immune ◽  
Antigen Uptake ◽  
Mhc Ii ◽  
Cell Functions ◽  
Cell Responses ◽  
Tnf Α ◽  
First Time ◽  
Priming Activity ◽  
Anti Inflammatory Cytokine

AbstractImmune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host's response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.

scholarly journals Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

2020 ◽  
Author(s):  
Christian Rodriguez Rodrigues ◽  
María Celeste Nicolao ◽  
Maia Chop ◽  
Natalia Plá ◽  
Mora Massaro ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Innate Immune ◽  
Antigen Uptake ◽  
Mhc Ii ◽  
Cell Functions ◽  
Cell Responses ◽  
Tnf Α ◽  
First Time ◽  
Priming Activity ◽  
Anti Inflammatory Cytokine

1.AbstractImmune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host’s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.

scholarly journals Microneme Proteins 1 and 4 From Toxoplasma gondii Induce IL-10 Production by Macrophages Through TLR4 Endocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Rafael Ricci-Azevedo ◽  
Flavia Costa Mendonça-Natividade ◽  
Ana Carolina Santana ◽  
Juliana Alcoforado Diniz ◽  
Maria Cristina Roque-Barreira
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Inflammatory Cytokine ◽  
Early Stage ◽  
Protozoan Parasite ◽  
Cell Responses ◽  
Tnf Α ◽  
Host Inflammatory Response ◽  
Anti Inflammatory Cytokine ◽  
Microneme Proteins

The protozoan parasite Toxoplasma gondii modulates host cell responses to favor its success in the early stage of infections by secreting proteins from its apical organelles. Some of these proteins, including microneme proteins (MICs) 1 and 4, trigger pro-inflammatory host cell responses. The lectins MIC1 and MIC4 interact with N-linked glycans on TLR2 and TLR4, activating NF-κB and producing IL-12, TNF-α, and IL-6. Interestingly, MIC1 and MIC4 also trigger secretion of the anti-inflammatory cytokine IL-10 through mechanisms as yet unknown. Herein, we show that the ability of these MICs to induce macrophages to produce IL-10 depends on TLR4 internalization from the cell surface. Macrophages subjected to blockade of endocytosis by Dynasore continued to release TNF-α, but failed to produce IL-10, in response to MIC1 or MIC4 exposure. Similarly, IL-10 was not produced by Dynasore-conditioned T. gondii-infected macrophages. Furthermore, MIC1- or MIC4-stimulated macrophages gained transient tolerance to LPS. We report a previously undiscovered mechanism by which well-defined T. gondii components inhibit a host inflammatory response.

scholarly journals The effect of macrophages polarization on the expression of oxytocin signaling system in enteric neurons

2021 ◽  
Author(s):  
Yao Shi ◽  
Shuang Li ◽  
Haojie Zhang ◽  
Jianchun Zhu ◽  
Tongtong Che ◽  
...  
Keyword(s):  
Enteric Neurons ◽  
Signaling System ◽  
M1 Macrophages ◽  
Macrophages Polarization ◽  
Tnf Α ◽  
First Time ◽  
Anti Inflammatory Cytokine ◽  
Colitis Model ◽  
M1 Type

Abstract Background: The aim of the current study is to investigate the effect of macrophages polarization on the expression of oxytocin (OT) and oxytocin receptor (OTR) in enteric neurons. Methods: In this study, we used a classic colitis model to observe the correlation between macrophages polarization and OT signaling system. In order to further demonstrate the effect of macrophages, we examined the expression of OT signaling system after depletion of macrophages. Results: The data showed that, in vitro, flowing macrophages polarization to M1 type by LPS, the macrophages supernatant inhibited the expression of OT and OTR in cultured enteric neurons through releasing pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α); flowing macrophages polarization to M2 type by IL4, the macrophages supernatant promoted the expression of OT and OTR in cultured enteric neurons through releasing anti-inflammatory cytokine (TGF-β). Furthermore, M1 macrophages decreased the expression of OT signaling system mainly through STAT3/NF-κB pathways in cultured enteric neurons; M2 macrophages increased expression of OT signaling system mainly through activation of Smad2/3 and inhibiting the expression of Peg3 in cultured enteric neurons. In DSS model, we demonstrated that macrophages were polarized to M1 type during the inflammatory phases, the expression of OT and OTR decreased significantly; and macrophages were polarized to M2 type during the recovery phases, the expression of OT and OTR increased significantly. At the same time, we also found that D-mannose increased the expression of OT and OTR through polarization of macrophages to M2 type. Conclusions: This is the first time to prove that the polarization of macrophages differentially regulates the expression of OT and OTR in enteric neurons.

scholarly journals Role of C-type Lectin Receptor to C.albicans on Promotion of Inflamantory Diseases

DENTA ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 63
Author(s):  
Erna Sulistyani
Keyword(s):  
Immune Cells ◽  
Inflammatory Diseases ◽  
Induce Polarization ◽  
Innate Immune ◽  
Oral Medicine ◽  
Lectin Receptor ◽  
Tnf Α ◽  
Transduction Signal ◽  
Anti Inflammatory Cytokine

<p><em>In early 2010 there was a very rapid progress in the development of immunity to fungi, i.e  the discovery of CLR. CLR is one of the PRR receptors found in immune cells that recognize the cell wall of fungi and then trigger a transduction signal that eventually provoke the production of various proinflamatory include IL1β, IL6, TNF α and induce polarization  Th17.  In the condition of infection the number of innate immune cells increases dramatically, lead to increasing of cytokines produced. Both cytokines and the cells that produce them enter the bloodstream. If there is unbalance level of pro and anti inflammatory cytokine, various inflammatory and/or autoimmune diseases can be occur. Unlike the focal concept infection, where the agent will cause disease if  enters the blood vessels, through this concept a fungal infection at epithelium can lead to inflammatory  diseases in other part of body without having to go through fungus</em></p><p><em> </em></p><p><strong><em>Keywords:</em></strong><em> C. albicans, CLR, Cytokine, Inflamatory Disease</em></p><p><strong><em> </em></strong></p><strong><em>Correspondence:  </em></strong><em>Erna Sulistyani, Department of Oral Medicine, Faculty of Dentistry, Jember Bagian Penyakit Mulut, Fakultas Kedokteran Gigi, Universitas Jember,  Kalimantan 37 Jember, Email: </em><a href="mailto:[email protected]"><em>[email protected]</em></a>

The Pattern of Acetylation Defines the Priming Activity of Chitosan Tetramers

2019 ◽  
Author(s):  
Sven Basa ◽  
Malathi Nampally ◽  
Talita Honorato ◽  
Subha Narayan Das ◽  
Appa Rao Podile ◽  
...  
Keyword(s):  
Biological Activity ◽  
Degree Of Polymerization ◽  
Chitosan Oligosaccharides ◽  
Degree Of Acetylation ◽  
Bona Fide ◽  
First Time ◽  
Priming Activity

The biological activity of chitosans depends on their degree of polymerization (DP) and degree of acetylation (DA). However, information could also be carried by the pattern of acetylation (PA): the sequence of <i>β</i>-1,4-linked glucosamine (deacetylated/D) and <i>N</i>-acetylglucosamine (acetylated/A) units. To address this hypothesis, we prepared partially-acetylated chitosan oligosaccharides from a chitosan polymer (DA=35%, DP<sub>w</sub>=905) using recombinant chitosan hydrolases with distinct substrate and cleavage specificities. The mixtures were separated into fractions DP4–DP12, which were tested for elicitor and priming activities in rice cells. We confirmed that both activities were influenced by DP, <a>but also observed apparent DA-dependent priming activity, with the ADDD+DADD fraction proving remarkably effective</a>. We then compared all four mono-acetylated tetramers prepared using different chitin deacetylases and observed significant differences in priming activity. This demonstrates for the first time that PA influences the biological activity of chitosans, which can now be recognized as <i>bona fide</i> information-carrying molecules

The Pattern of Acetylation Defines the Priming Activity of Chitosan Tetramers

2019 ◽  
Author(s):  
Sven Basa ◽  
Malathi Nampally ◽  
Talita Honorato ◽  
Subha Narayan Das ◽  
Appa Rao Podile ◽  
...  
Keyword(s):  
Biological Activity ◽  
Degree Of Polymerization ◽  
Chitosan Oligosaccharides ◽  
Degree Of Acetylation ◽  
Bona Fide ◽  
First Time ◽  
Priming Activity

The biological activity of chitosans depends on their degree of polymerization (DP) and degree of acetylation (DA). However, information could also be carried by the pattern of acetylation (PA): the sequence of <i>β</i>-1,4-linked glucosamine (deacetylated/D) and <i>N</i>-acetylglucosamine (acetylated/A) units. To address this hypothesis, we prepared partially-acetylated chitosan oligosaccharides from a chitosan polymer (DA=35%, DP<sub>w</sub>=905) using recombinant chitosan hydrolases with distinct substrate and cleavage specificities. The mixtures were separated into fractions DP4–DP12, which were tested for elicitor and priming activities in rice cells. We confirmed that both activities were influenced by DP, <a>but also observed apparent DA-dependent priming activity, with the ADDD+DADD fraction proving remarkably effective</a>. We then compared all four mono-acetylated tetramers prepared using different chitin deacetylases and observed significant differences in priming activity. This demonstrates for the first time that PA influences the biological activity of chitosans, which can now be recognized as <i>bona fide</i> information-carrying molecules

scholarly journals Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients

2021 ◽  
Author(s):  
Vasiliki Courelli ◽  
Alla Ahmad ◽  
Majid Ghassemian ◽  
Chris Pruitt ◽  
Paul J. Mills ◽  
...  
Keyword(s):  
Heart Failure ◽  
Digestive Enzymes ◽  
Digestive Enzyme ◽  
Myocardial Cell ◽  
Systemic Circulation ◽  
Tissue Destruction ◽  
Cell Functions ◽  
Tnf Α ◽  
Elevated Activity ◽  
Trigger Mechanisms

Abstract Introduction Heart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure. Methods Accordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion. Results Western analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with the cardiac dysfunction biomarker BNP and inflammatory biomarkers CRP and TNF-α. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of plasma proteins in the HF patients is similar to controls while the number of peptides was increased about 20% in HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases (data are available via ProteomeXchange with identifier PXD026332). Connclusions These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. Conclusions These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients.

scholarly journals Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuxuan Li ◽  
Yang Jie ◽  
Xiaofei Wang ◽  
Jing Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Medical Records ◽  
Clinical Information ◽  
Serum Cytokines ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Ifn Γ ◽  
Quantitative Changes ◽  
Anti Inflammatory Cytokine

Abstract Background Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA. Results The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI. Conclusions Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

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