scholarly journals Candida albicans Is Phagocytosed, Killed, and Processed for Antigen Presentation by Human Dendritic Cells

2001 ◽  
Vol 69 (11) ◽  
pp. 6813-6822 ◽  
Author(s):  
Simon L. Newman ◽  
Angela Holly
Keyword(s):  
Dendritic Cells ◽  
Candida Albicans ◽  
Invasive Fungal Disease ◽  
Interleukin 4 ◽  
Cell Mediated Immunity ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Human Dendritic Cells

ABSTRACT Candida albicans is a component of the normal flora of the alimentary tract and also is found on the mucocutaneous membranes of the healthy host. Candida is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients, and of oropharyngeal disease in AIDS patients. As the induction of cell-mediated immunity to Candida is of critical importance in host defense, we sought to determine whether human dendritic cells (DC) could phagocytose and degradeCandida and subsequently present Candidaantigens to T cells. Immature DC obtained by culture of human monocytes in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 phagocytosed unopsonized Candida in a time-dependent manner, and phagocytosis was not enhanced by opsonization of Candida in serum. Like macrophages (Mφ), DC recognized Candida by the mannose-fucose receptor. Upon ingestion, DC killed Candida as efficiently as human Mφ, and fungicidal activity was not enhanced by the presence of fresh serum. Although phagocytosis ofCandida by DC stimulated the production of superoxide anion, inhibitors of the respiratory burst (or NO production) did not inhibit killing of Candida, even when phagocytosis was blocked by preincubation of DC with cytochalasin D. Further, although apparently only modest phagolysosomal fusion occurred upon DC phagocytosis of Candida, killing ofCandida under anaerobic conditions was almost equivalent to killing under aerobic conditions. Finally, DC stimulatedCandida-specific lymphocyte proliferation in a concentration-dependent manner after phagocytosis of both viable and heat-killed Candida cells. These data suggest that, in vivo, such interactions between DC and C. albicans may facilitate the induction of cell-mediated immunity.

scholarly journals A Monocyte Conditioned Medium Is More Effective Than Defined Cytokines in Mediating the Terminal Maturation of Human Dendritic Cells

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3640-3646 ◽  
Author(s):  
Anita Reddy ◽  
Mark Sapp ◽  
Mary Feldman ◽  
Marion Subklewe ◽  
Nina Bhardwaj
Keyword(s):  
Dendritic Cells ◽  
Conditioned Medium ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Interferon Α ◽  
Mature Phase ◽  
Macrophage Colony ◽  
Factor Α ◽  
Human Dendritic Cells

Abstract Mature human dendritic cells can be generated in substantial numbers from nonproliferating progenitors in human blood using a two-step protocol. T cell–depleted mononuclear cells are first cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) and then exposed to monocyte conditioned medium (MCM). The dendritic cells generated using this approach are rendered terminally mature and are the most potent antigen presenting cells identified to date in humans. We sought to characterize factors in MCM that induce the terminal differentiation of dendritic cells. MCM contained substantial, although varying, quantities of several factors including tumor necrosis factor-α, IL-1β, IL-6, and interferon-α. However, none of the four factors, individually or in various combinations, could fully substitute for the MCM to generate irreversibly differentiated dendritic cells. The yields, percentage of cells expressing the mature phase marker CD83, and mixed leukocyte reaction–stimulatory function were lower when defined cytokines were used in the place of MCM. Therefore, the full maturation of dendritic cells, because it entails changes in many known cell and molecular properties, requires a number of different cytokines that are released in tandem from appropriately stimulated monocytes. We propose that MCM-matured dendritic cells will be the most effective adjuvants for immunotherapy in vivo.

scholarly journals Cilostazol Suppresses IL-23 Production in Human Dendritic Cells via an AMPK-Dependent Pathway

2016 ◽  
Vol 40 (3-4) ◽  
pp. 499-508 ◽  
Author(s):  
Quanxing Shi ◽  
Zhao Yin ◽  
Peilin Liu ◽  
Bei Zhao ◽  
Zhong Zhang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Western Blotting ◽  
Human Monocyte ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Compound C ◽  
Human Dendritic Cells ◽  
Dependent Pathway

Background/Aims: Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms. Methods: Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan. Enzyme-linked immunosorbent assay (ELISA) and real time PCR analyses were used to measure IL-23 protein expression and RNA levels, respectively, whereas Western blotting was used to measure the expression and phosphorylation level of AMPK. Results: Our results demonstrated that cilostazol suppressed zymosan-induced IL-23 protein production in a concentration dependent manner without affecting dendritic cell viability. In addition, it was found that cilostazol suppressed the expression of the p19 and p40 subunits of IL-23. Moreover, cilostazol mimicked the effect of the AMPK agonist A-769662, as demonstrated by the fact that IL-23 production was also inhibited by A-769662, and the effect of cilostazol on IL-23 production was blocked by the AMPK antagonist Compound C. More importantly, Western blotting demonstrated that cilostazol led to an increased phosphorylation of AMPK. Conclusion: Collectively, our data suggest that cilostazol inhibits the production of IL-23 in human mo-DCs, potentially via the activation of AMPK. This suggests that cilostazol could be an effective anti-inflammatory agent in IL-23- and dendritic cell-related diseases.

scholarly journals Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 563
Author(s):  
Maximilian Fellermann ◽  
Christina Huchler ◽  
Lea Fechter ◽  
Tobias Kolb ◽  
Fanny Wondany ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stimulated Emission ◽  
Target Cells ◽  
Dependent Manner ◽  
Rho Proteins ◽  
Concentration Dependent Manner ◽  
Monocytic Cells ◽  
Specific Uptake ◽  
Novel Target ◽  
Human Dendritic Cells

C3 protein toxins produced by Clostridium (C.) botulinum and C. limosum are mono-ADP-ribosyltransferases, which specifically modify the GTPases Rho A/B/C in the cytosol of monocytic cells, thereby inhibiting Rho-mediated signal transduction in monocytes, macrophages, and osteoclasts. C3 toxins are selectively taken up into the cytosol of monocytic cells by endocytosis and translocate from acidic endosomes into the cytosol. The C3-catalyzed ADP-ribosylation of Rho proteins inhibits essential functions of these immune cells, such as migration and phagocytosis. Here, we demonstrate that C3 toxins enter and intoxicate dendritic cells in a time- and concentration-dependent manner. Both immature and mature human dendritic cells efficiently internalize C3 exoenzymes. These findings could also be extended to the chimeric fusion toxin C2IN-C3lim. Moreover, stimulated emission depletion (STED) microscopy revealed the localization of the internalized C3 protein in endosomes and emphasized its potential use as a carrier to deliver foreign proteins into dendritic cells. In contrast, the enzyme C2I from the binary C. botulinum C2 toxin was not taken up into dendritic cells, indicating the specific uptake of C3 toxins. Taken together, we identified human dendritic cells as novel target cells for clostridial C3 toxins and demonstrated the specific uptake of these toxins via endosomal vesicles.

scholarly journals PGE2 Elevates IL-23 Production in Human Dendritic Cells via a cAMP Dependent Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Quanxing Shi ◽  
Zhao Yin ◽  
Bei Zhao ◽  
Fei Sun ◽  
Haisheng Yu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Concentration Dependent Manner ◽  
Underlying Mechanisms ◽  
Species Specific ◽  
Human Dendritic Cells ◽  
Dependent Pathway ◽  
Cyclase Activator

PGE2 elevates IL-23 production in mouse dendritic cells while inhibits IL-23 production in isolated human monocytes. Whether this differential effect of PGE2 on IL-23 production is cell-type- or species-specific has not been investigated in detail. The present study was designed to investigate the effect of PGE2 on IL-23 production in human DCs and the possible underlying mechanisms. Human monocytes derived dendritic cells (Mo-DCs) were pretreated with or without PGE2. Then the cells were incubated with zymosan. Our results demonstrated that PGE2 promoted zymosan-induced IL-23 production in a concentration dependent manner. In addition, it was found that PGE2 is also able to elevate MyD88-mediated IL-23 p19 promoter activity. More importantly, ELISA data demonstrated that db-cAMP, a cAMP analog, and forskolin, an adenylate cyclase activator, can mimic the effect of PGE2 on zymosan-induced IL-23 production, and rp-cAMP, a protein kinase A (PKA) inhibitor, can block the effect of PGE2. Moreover, PGE2 can increase zymosan-induced expression of the mRNA levels of both p19 and p40 subunits, which was mimicked by db-cAMP and forskolin. Our data suggest that PGE2 elevates the production of IL-23 in human Mo-DCs via a cAMP dependent pathway.

scholarly journals Cholera Toxin Impairs the Differentiation of Monocytes into Dendritic Cells, Inducing Professional Antigen-Presenting Myeloid Cells

2010 ◽  
Vol 79 (3) ◽  
pp. 1300-1310 ◽  
Author(s):  
Filippo Veglia ◽  
Ester Sciaraffia ◽  
Antonella Riccomi ◽  
Dora Pinto ◽  
Donatella R. M. Negri ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cholera Toxin ◽  
Interleukin 4 ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Class I Mhc ◽  
Mhc I ◽  
Antigen Presenting

ABSTRACTCholera toxin (CT) is a potent adjuvant for mucosal vaccination; however, its mechanism of action has not been clarified completely. It is well established that peripheral monocytes differentiate into dendritic cells (DCs) bothin vitroandin vivoand that monocytes are thein vivoprecursors of mucosal CD103−proinflammatory DCs. In this study, we asked whether CT had any effects on the differentiation of monocytes into DCs. We found that CT-treated monocytes, in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), failed to differentiate into classical DCs (CD14lowCD1ahigh) and acquired a macrophage-like phenotype (CD14highCD1alow). Cells differentiated in the presence of CT expressed high levels of major histocompatibility complex class I (MHC-I) and MHC-II and CD80 and CD86 costimulatory molecules and produced larger amounts of IL-1β, IL-6, and IL-10 but smaller amounts of tumor necrosis factor alpha (TNF-α) and IL-12 than did monocytes differentiated into DCs in the absence of CT. The enzymatic activity of CT was found to be important for the skewing of monocytes toward a macrophage-like phenotype (Ma-DCs) with enhanced antigen-presenting functions. Indeed, treatment of monocytes with scalar doses of forskolin (FSK), an activator of adenylate cyclase, induced them to differentiate in a dose-dependent manner into a population with phenotype and functions similar to those found after CT treatment. Monocytes differentiated in the presence of CT induced the differentiation of naïve T lymphocytes toward a Th2 phenotype. Interestingly, we found that CT interferes with the differentiation of monocytes into DCsin vivoand promotes the induction of activated antigen-presenting cells (APCs) following systemic immunization.

Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells

Blood ◽  
2012 ◽  
Vol 119 (20) ◽  
pp. 4636-4644 ◽  
Author(s):  
Qianqian Shao ◽  
Hao Ning ◽  
Jiaju Lv ◽  
Yanguo Liu ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Costimulatory Molecule ◽  
Autoimmune Disorder ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Dependent Manner ◽  
Tissue Inhibitor ◽  
Th2 Polarization ◽  
Human Dendritic Cells

Abstract Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder–primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

scholarly journals Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1545
Author(s):  
Hwa-Young Song ◽  
Da-Eun Jeong ◽  
Mina Lee
Keyword(s):  
Biological Activities ◽  
Radical Scavenging ◽  
No Production ◽  
Dependent Manner ◽  
Optimal Method ◽  
Concentration Dependent Manner ◽  
Osmanthus Fragrans ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

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