scholarly journals Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformansIn VitroRequires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

2016 ◽  
Vol 84 (9) ◽  
pp. 2493-2504 ◽  
Author(s):  
Camaron R. Hole ◽  
Chrissy M. Leopold Wager ◽  
Andrew S. Mendiola ◽  
Karen L. Wozniak ◽  
Althea Campuzano ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dendritic Cells ◽  
Pulmonary Infection ◽  
Reactive Oxygen ◽  
Optimal Growth ◽  
Plasmacytoid Dendritic Cells ◽  
Oxygen Species ◽  
Content Type ◽  
Lectin Receptor

Conventional dendritic cells (cDCs) are critical for protection against pulmonary infection with the opportunistic fungal pathogenCryptococcus neoformans; however, the role of plasmacytoid dendritic cells (pDCs) is unknown. We show for the first time that murine pDCs have direct activity againstC. neoformansvia reactive oxygen species (ROS), a mechanism different from that employed to controlAspergillus fumigatusinfections. The anticryptococcal activity of murine pDCs is independent of opsonization but appears to require the C-type lectin receptor Dectin-3, a receptor not previously evaluated during cryptococcal infections. Human pDCs can also inhibit cryptococcal growth by a mechanism similar to that of murine pDCs. Experimental pulmonary infection of mice with aC. neoformansstrain that induces protective immunity demonstrated that recruitment of pDCs to the lungs is CXCR3 dependent. Taken together, our results show that pDCs inhibitC. neoformansgrowthin vitrovia the production of ROS and that Dectin-3 is required for optimal growth-inhibitory activity.

scholarly journals High inductive magnetic stimuli and their effects on mesenchymal stromal cells, dendritic cells, and fibroblasts

2019 ◽  
pp. S433-S443
Author(s):  
J. Průcha ◽  
J. Skopalik ◽  
I. Justan ◽  
T. Parák ◽  
E. Gabrielová ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dendritic Cells ◽  
Cell Migration ◽  
Electromagnetic Fields ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Functional Changes

Effects of low-frequency electromagnetic fields (LF EMF) on the activation of different tissue recovery processes have already been fully understood. Preliminary recent data demonstrated that a special case of sinusoidal electromagnetic fields, known as amplitude-modulated currents (AMC) could have a potential to accelerate the cell metabolism or cell migration. An AMC generator was designed to generate sinusoidal induced electric currents with the amplitude modulation and the harmonic carrier frequency of 5,000 Hz was modulated by frequencies of 1 to 100 Hz. The magnetic field peak was 6 mT, electric field intensity 2 V/m and the current density of induced electrical currents was approximately 1 A/m2. The coil of the generator was adapted to easy handling and safe integration into the shelf of the CO2 incubator. The shelf with the coil was prepared for the introduction of cells in standard plastic in vitro chambers. The tests focused on cells with migratory capacity after injury or during immunological processes and thus, mesenchymal stromal cells (MSC), dendritic cells (DC), and fibroblasts were chosen. The tests involved exposures of the cells to LF EMF (180 min/day) every day, for a period of three days, before examining them for cell death, morphology changes, and CD markers. The samples were tested by using MTT assay and the effects on the intracellular concentration of reactive oxygen species were quantified. The cell migration was finally measured with the help of the transwell migration assay. None of the cell types showed any decrease in the cell viability after the LF EMF application and the cells displayed minimum changes in reactive oxygen species. Functional changes (acceleration of cell migration) after AMC exposure were statistically significant for the MSC samples only. The acceleration of MSCs is associated with the production of MMP by these cells. The EMF has a potential to be a safe, clinically applicable selective activator of MSC homing, MSC paracrine production, and subsequent regeneration processes.

scholarly journals The Small GTPase RacA Mediates Intracellular Reactive Oxygen Species Production, Polarized Growth, and Virulence in the Human Fungal Pathogen Aspergillus fumigatus

2010 ◽  
Vol 10 (2) ◽  
pp. 174-186 ◽  
Author(s):  
Haiyan Li ◽  
Bridget M. Barker ◽  
Nora Grahl ◽  
Srisombat Puttikamonkul ◽  
Jeremey D. Bell ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Aspergillus Fumigatus ◽  
Invasive Pulmonary Aspergillosis ◽  
Reactive Oxygen ◽  
Small Gtpase ◽  
Oxygen Species ◽  
Wild Type ◽  
Content Type ◽  
Diphenylene Iodonium

ABSTRACTAspergillus fumigatusis the predominant mold pathogen in immunocompromised patients. In this study, we present the first characterization of the small GTPase RacA inA. fumigatus. To gain insight into the function ofracAin the growth and pathogenesis ofA. fumigatus, we constructed a strain that lacks a functionalracAgene. The ΔracAstrain showed significant morphological defects, including a reduced growth rate and abnormal conidiogenesis on glucose minimal medium. In the ΔracAstrain, apical dominance in the leading hyphae is lost and, instead, multiple axes of polarity emerge. Intriguingly, superoxide production at the hyphal tips was reduced by 25% in the ΔracAstrain. Treatment of wild-type hyphae with diphenylene iodonium, an inhibitor of NADPH oxidase, resulted in phenotypes similar to that of the ΔracAstrain. These data suggest that ΔracAstrain phenotypes may be due to a reduction or alteration in the production of reactive oxygen species. Most surprisingly, despite these developmental and growth abnormalities, the ΔracAstrain retained at least wild-type virulence in both an insect model and two immunologically distinct murine models of invasive pulmonary aspergillosis. These results demonstrate thatin vitrogrowth phenotypes do not always correlate within vivovirulence and raise intriguing questions about the role of RacA inAspergillusvirulence.

scholarly journals Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Marine Oberkampf ◽  
Camille Guillerey ◽  
Juliette Mouriès ◽  
Pierre Rosenbaum ◽  
Catherine Fayolle ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Reactive Oxygen ◽  
Plasmacytoid Dendritic Cells ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species

scholarly journals Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

2012 ◽  
Vol 12 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Claudia Jiménez-López ◽  
John R. Collette ◽  
Kimberly M. Brothers ◽  
Kelly M. Shepardson ◽  
Robert A. Cramer ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Candida Albicans ◽  
Amino Acid ◽  
Reactive Oxygen ◽  
Single Amino Acid ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Biosynthetic Genes ◽  
Content Type

ABSTRACTThe interaction ofCandida albicanswith phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvationin vitroand is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations.C. albicanscells phagocytosed by primary macrophages deficient in thegp91phoxsubunit of the phagocyte oxidase do not express theARGpathway, indicating that the induction is dependent on the phagocyte oxidative burst.C. albicans argpathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that theARGpathway is regulated not by the general amino acid control response but by transcriptional regulators similar to theSaccharomyces cerevisiaeArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.

scholarly journals Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

2013 ◽  
Vol 57 (9) ◽  
pp. 4360-4368 ◽  
Author(s):  
Fazal Shirazi ◽  
Michael A. Pontikos ◽  
Thomas J. Walsh ◽  
Nathaniel Albert ◽  
Russell E. Lewis ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Rhizopus Oryzae ◽  
Reactive Oxygen ◽  
Annexin V ◽  
Intracellular Reactive Oxygen Species ◽  
Oxygen Species ◽  
Content Type ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition

ABSTRACTThe high mortality rate of mucormycosis with currently available monotherapy has created interest in studying novel strategies for antifungal agents. With the exception of amphotericin B (AMB), the triazoles (posaconazole [PCZ] and itraconazole [ICZ]) are fungistaticin vitroagainstRhizopus oryzae. We hypothesized that growth at a high temperature (42°C) results in fungicidal activity of PCZ and ICZ that is mediated through apoptosis.R. oryzaehad high MIC values for PCZ and ICZ (16 to 64 μg/ml) at 25°C; in contrast, the MICs for PCZ and ICZ were significantly lower at 37°C (8 to 16 μg/ml) and 42°C (0.25 to 1 μg/ml). Furthermore, PCZ and ICZ dose-dependent inhibition of germination was more pronounced at 42°C than at 37°C. In addition, intracellular reactive oxygen species (ROS) increased significantly when fungi were exposed to antifungals at 42°C. Characteristic cellular changes of apoptosis inR. oryzaewere induced by the accumulation of intracellular reactive oxygen species. Cells treated with PCZ or ICZ in combination with hyperthermia (42°C) exhibited characteristic markers of early apoptosis: phosphatidylserine externalization visualized by annexin V staining, membrane depolarization visualized by bis-[1,3-dibutylbarbituric acid] trimethine oxonol (DiBAC) staining, and increased metacaspase activity. Moreover, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and DAPI (4′,6-diamidino-2-phenylindole) staining demonstrated DNA fragmentation and condensation, respectively. The addition ofN-acetylcysteine increased fungal survival, prevented apoptosis, reduced ROS accumulation, and decreased metacaspase activation. We concluded that hyperthermia, either alone or in the presence of PCZ or ICZ, induces apoptosis inR. oryzae. Local thermal delivery could be a therapeutically useful adjunct strategy for these refractory infections.

scholarly journals Regulation of type I interferon responses by mitochondria-derived reactive oxygen species in plasmacytoid dendritic cells

Redox Biology ◽  
2017 ◽  
Vol 13 ◽  
pp. 633-645 ◽  
Author(s):  
Zsofia Agod ◽  
Tünde Fekete ◽  
Marietta M. Budai ◽  
Aliz Varga ◽  
Attila Szabo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dendritic Cells ◽  
Type I Interferon ◽  
Reactive Oxygen ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Oxygen Species ◽  
Interferon Responses

scholarly journals The Effects of Bioactive Compounds from Blueberry and Blackcurrant Powder on Oat Bran Pastes: Enhancing In Vitro Antioxidant Activity and Reducing Reactive Oxygen Species in Lipopolysaccharide-Stimulated Raw264.7 Macrophages

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 388
Author(s):  
Xiao Dan Hui ◽  
Gang Wu ◽  
Duo Han ◽  
Xi Gong ◽  
Xi Yang Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antioxidant Activity ◽  
Phenolic Compounds ◽  
Antioxidant Capacity ◽  
Bioactive Compounds ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Raw264.7 Macrophages ◽  
Oat Bran

In this study, blueberry and blackcurrant powder were chosen as the phenolic-rich enrichments for oat bran. A Rapid Visco Analyser was used to form blueberry and blackcurrant enriched oat pastes. An in vitro digestion process evaluated the changes of phenolic compounds and the in vitro antioxidant potential of extracts of pastes. The anthocyanidin profiles in the extracts were characterised by the pH differential method. The results showed that blueberry and blackcurrant powder significantly increased the content of phenolic compounds and the in vitro antioxidant capacity of pastes, while the total flavonoid content decreased after digestion compared to the undigested samples. Strong correlations between these bioactive compounds and antioxidant values were observed. Lipopolysaccharide-stimulated RAW264.7 macrophages were used to investigate the intracellular antioxidant activity of the extracts from the digested oat bran paste with 25% enrichment of blueberry or blackcurrant powder. The results indicated that the extracts of digested pastes prevented the macrophages from experiencing lipopolysaccharide (LPS)-stimulated intracellular reactive oxygen species accumulation, mainly by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway. These findings suggest that the bioactive ingredients from blueberry and blackcurrant powder enhanced the in vitro and intracellular antioxidant capacity of oat bran pastes, and these enriched pastes have the potential to be utilised in the development of the functional foods.

scholarly journals Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhuochao Liu ◽  
Hongyi Wang ◽  
Chuanzhen Hu ◽  
Chuanlong Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antitumor Immunity ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Specific Monoclonal Antibody ◽  
Osteosarcoma Cells ◽  
Jnk Pathway ◽  
In Vivo Experiments

AbstractIn this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

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