scholarly journals Regulation of Transcription Factor E2-2 in Human Plasmacytoid Dendritic Cells by Monocyte-Derived TNFα

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 162 ◽  
Author(s):  
Hannah K. Dewald ◽  
Harry J. Hurley ◽  
Patricia Fitzgerald-Bocarsly
Keyword(s):  
Dendritic Cells ◽  
Transcription Factor ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Plasmacytoid Dendritic Cells ◽  
Cytokine Signaling ◽  
Regulation Of Transcription ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Altered Expression

Plasmacytoid dendritic cells (pDCs) are innate immune cells and potent producers of interferon alpha (IFNα). Regulation of pDCs is crucial for prevention of aberrant IFN production. Transcription factor E2-2 (TCF4) regulates pDC development and function, but mechanisms of E2-2 control have not been investigated. We used freshly-isolated human peripheral blood mononuclear cells stimulated with toll-like receptor 7, 9, and 4 agonists to determine which factors regulate E2-2. After activation, pDCs decreased E2-2 expression. E2-2 downregulation occurred during the upregulation of costimulatory markers, after maximal IFN production. In congruence with previous reports in mice, we found that primary human pDCs that maintained high E2-2 levels produced more IFN, and had less expression of costimulatory markers. Stimulation of purified pDCs did not lead to E2-2 downregulation; therefore, we investigated if cytokine signaling regulates E2-2 expression. We found that tumor necrosis factor alpha (TNFα) produced by monocytes caused decreased E2-2 expression. All together, we established that primary human pDCs decrease E2-2 in response to TNFα and E2-2 low pDCs produce less IFN but exhibit more costimulatory molecules. Altered expression of E2-2 may represent a mechanism to attenuate IFN production and increase activation of the adaptive immune compartment.

scholarly journals Differential In Vitro Cytokine Induction by the Species of Cryptococcus gattii Complex

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Patricia F. Herkert ◽  
Jessica C. dos Santos ◽  
Ferry Hagen ◽  
Fatima Ribeiro-Dias ◽  
Flávio Queiroz-Telles ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Sensu Stricto ◽  
Cryptococcus Gattii ◽  
The Other ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α

ABSTRACT Cryptococcal species vary in capsule and cell size, thermotolerance, geographic distribution, and affected populations. Cryptococcus gattii sensu stricto and C. deuterogattii affect mainly immunocompetent hosts; however, C. bacillisporus , C. decagattii , and C. tetragattii cause infections mainly in immunocompromised hosts. This study aimed to compare the capacities of different species of the C. gattii species complex to induce cytokines and antimicrobial molecules in human peripheral blood mononuclear cells (PBMCs). Cryptococcus bacillisporus and C. deuterogattii induced the lowest levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 among the five species of the C. gattii complex. Cryptococcus deuterogattii induced higher levels of IL-22 than those induced by C. tetragattii and the environmental species C. flavescens . In addition, C. bacillisporus and C. gattii sensu stricto proliferated inside human monocyte-derived macrophages after 24 h of infection. All Cryptococcus species were able to generate reactive oxygen species (ROS) in human PBMCs, with C. bacillisporus and C. deuterogattii being more efficient than the other species. In conclusion, C. bacillisporus and C. deuterogattii induce lower levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and higher ROS levels than those induced by the other species. Species of the Cryptococcus gattii complex have different abilities to induce cytokine and ROS production by human PBMCs.

Immunopotent Polysaccharides of Different Sources Selectively Activate Human Dendritic Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3873-3873
Author(s):  
Godfrey ChiFung Chan ◽  
W.K. Chan ◽  
H.K. Law ◽  
Z.B. Lin ◽  
Y.L. Lau
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
T Helper ◽  
T Helper 1 ◽  
Xtt Assay ◽  
Peripheral Blood Mononuclear ◽  
Human Dendritic Cells

Abstract Background: Purified polysaccharides extracted from plants and fungi have been shown to induce immune responses in-vivo and vitro over the past decade. Currently, most of these polysaccharides are found to be glucan but with different branch structure and sizes. Their relative potency and effect on human immune cells remains unknown. This study aims to compare their relative effect on human dendritic cell, the most potent antigen presenting cell. Materials & Methods: We selected 2 prototypes of purified polysaccharides extracted from: 1) Ganoderma lucidum (GL, Lingzhi, Reishi) mycelium, a widely used herb with long and branching β (1® 3), (1® 6) glucan structure (provided by Prof. Lin ZB, Beijing) and 2) Barley with shorter and different branching β (1® 3), (1® 4) structure (provided by Prof. Cheung VNK, NY). Their characteristics and chemical properties had been reported previously. Human peripheral blood mononuclear cells (PBMCs) proliferation was studied by XTT assay. Human dendritic cells (DCs) were derived from monocytes and maturation of DCs were determined by: a) immunophenotypic shift using flow cytometer; 2) dextran endocytosis assay and 3) mixed lymphocytes reaction. Cytokine secretions were determined by ELISA test. Comparisons between means were by nonparametric Student’s t test (2-tailed). Results: We found that purified polysaccharides from GL but not barley could induce PBMCs proliferation and maturation of DCs. GL polysaccharides could enhance phenotypic and functional maturation of DCs with significant IL-12 and IL-10 production. DCs were relatively inert to Barley glucans stimulation. However, both polysaccharides did not polarize T cells into the direction of T helper 1, T helper 2 or regulatory T cells. Conclusions: Our study shown that purified polysaccharides extracted from plants and fungi have different effect on human DCs and their potency and effects are probably affected by their respective sources and structures.

Inhibition Of S100A6 Induces Graft Versus Leukemia Effects In MLL/AF4-Positive ALL In Human PBMC-SCID Mice

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2016-2016
Author(s):  
Hayato Tamai ◽  
Hiroki Yamaguchi ◽  
Kazuo Dan ◽  
Koiti Inokuchi
Keyword(s):  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Human Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Scid Mice ◽  
Long Term Effects ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Hematopoietic Stem ◽  
Graft Versus Leukemia

Mixed-lineage leukemia (MLL)/AF4-positive acute lymphoblastic leukemia (ALL) is associated with poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The resistance to graft-versus-leukemia (GVL) effects may be responsible for the poor effect of allo-HSCT on MLL-AF4-positive ALL. Cytotoxic effector mechanisms mediated by tumor necrosis factor-alpha (TNF-a) was reported to contribute to the GVL effect. We reported previously that MLL/AF4-positive ALL shows resistance to TNF-a, which is the main factor in GVL effect, by upregulation of S100A6 expression followed by interference with the p53-caspase 8-caspase 3 pathway in vitro. We examined whether inhibition of S100A6 can induce an effective GVL effect on MLL/AF4-positive ALL in a mouse model. To examine the long-term effects of inhibition of S100A6,MLL/AF4-positive ALL cell lines (SEM) transduced with lentiviral vectors expressing both S100A6 siRNA and luciferase (SEM-Luc-S100A6 siRNA) were produced. SEM-Luc-S100A6 siRNA cells and SEM-Luc-control siRNA cells were injected into groups of five SCID mice (1×107/body). After confirmation of engraftment of SEM cells by in vivo imaging, the mice in each group were injected with 4.8×107 human peripheral blood mononuclear cells (PBMCs). Although there were no significant differences between the serum concentrations of human-TNF-a after injection of human PBMCs of SEM-Luc-S100A6 siRNA injected mice and those of SEM-Luc-control siRNA injected mice (P=0.95), SEM-Luc-S100A6 siRNA-injected mice showed significantly longer survival periods than SEM-Luc-control siRNA-injected mice (P = 0.002). SEM-Luc-S100A6 siRNA-injected mice showed significantly slower tumor growth than those injected with SEM-Luc-control siRNA (P < 0.0001). These results suggested that inhibition of S100A6 may be a promising therapeutic target for MLL/AF4-positive ALL in combination with allo-HSCT because it induce effective GVL effectson MLL/AF4-positive ALL which is resistant to GVL effects. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Interaction of Rotavirus with Human Myeloid Dendritic Cells

2005 ◽  
Vol 79 (23) ◽  
pp. 14526-14535 ◽  
Author(s):  
Carlos F. Narváez ◽  
Juana Angel ◽  
Manuel A. Franco
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Transforming Growth Factor Beta ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Myeloid Dendritic Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Stimulation Of

ABSTRACT We have previously shown that very few rotavirus (RV)-specific T cells that secrete gamma interferon circulate in recently infected and seropositive adults and children. Here, we have studied the interaction of RV with myeloid immature (IDC) and mature dendritic cells (MDC) in vitro. RV did not induce cell death of IDC or MDC and induced maturation of between 12 and 48% of IDC. Nonetheless, RV did not inhibit the maturation of IDC or change the expression of maturation markers on MDC. After treatment with RV, few IDC expressed the nonstructural viral protein NSP4. In contrast, a discrete productive viral infection was shown in MDC of a subset of volunteers, and between 3 and 46% of these cells expressed NSP4. RV-treated IDC secreted interleukin 6 (IL-6) (but not IL-1β, IL-8, IL-10, IL-12, tumor necrosis factor alpha, or transforming growth factor beta), and MDC released IL-6 and small amounts of IL-10 and IL-12p70. The patterns of cytokines secreted by T cells stimulated by staphylococcal enterotoxin B presented by MDC infected with RV or uninfected were comparable. The frequencies and patterns of cytokines secreted by memory RV-specific T cells evidenced after stimulation of peripheral blood mononuclear cells (PBMC) with RV were similar to those evidenced after stimulation of PBMC with RV-infected MDC. Finally, IDC treated with RV strongly stimulated naive allogeneic CD4+ T cells to secrete Th1 cytokines. Thus, although RV does not seem to be a strong maturing stimulus for DC, it promotes their capacity to prime Th1 cells.

scholarly journals Induction of Cytokine Synthesis by Flagella from Gram-Negative Bacteria May Be Dependent on the Activation or Differentiation State of Human Monocytes

1999 ◽  
Vol 67 (10) ◽  
pp. 5176-5185 ◽  
Author(s):  
Federica Ciacci-Woolwine ◽  
Patrick F. McDermott ◽  
Steven B. Mizel
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Substantial Effect ◽  
Gram Negative Bacteria ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
E Coli ◽  
Cytokine Synthesis ◽  
Normal Human Peripheral Blood

ABSTRACT We have previously demonstrated that salmonellae, but notEscherichia coli or Yersinia enterocolitica, stimulates tumor necrosis factor alpha (TNFα) production in the human promonocytic cell line U38. Subsequent analysis revealed that the TNFα-inducing activity of salmonellae was associated with flagellin, a major component of flagella from gram-negative bacteria. In the present study, we have explored the basis for the apparent specificity of action of Salmonella flagella on TNFα expression in U38 cells and have extended this analysis to normal human peripheral blood mononuclear cells (PBMC). Flagella from the enteropathogenicE. coli strain E2348/69, Y. enterocoliticaJB580, and Pseudomonas aeruginosa PAO1, which did not induce significant levels of TNFα production in U38 cells, were as potent as Salmonella flagella in terms of TNFα and interleukin 1β activation in PBMC. However, TNFα production in U38 cells was greatly enhanced when these cells were stimulated with flagella from E. coli, Y. enterocolitica, andP. aeruginosa in the presence of a costimulant, phorbol 13-myristate acetate. These findings are consistent with the hypothesis that the activation or differentiation state of a monocyte may have a substantial effect on the cell’s responsiveness to flagellum stimulation of cytokine synthesis. Furthermore, these results indicate that cytokine induction in monocytes may be a general property of flagella from gram-negative bacteria.

scholarly journals Adjuvant Activity of Synthetic Lipid A of Alcaligenes, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 395 ◽  
Author(s):  
Yunru Wang ◽  
Koji Hosomi ◽  
Atsushi Shimoyama ◽  
Ken Yoshii ◽  
Haruki Yamaura ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Lipid A ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
T Helper ◽  
T Helper 17 ◽  
Adjuvant Activity ◽  
Peripheral Blood Mononuclear ◽  
Specific Igg

Alcaligenes spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that Alcaligenes-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized Alcaligenes lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus Alcaligenes lipid A relative to those that were immunized with OVA alone. In addition, Alcaligenes lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with Alcaligenes lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, Alcaligenes lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that Alcaligenes lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.

scholarly journals Immunomodulating Properties of the Antibiotic Novobiocin in Human Monocytes

1998 ◽  
Vol 42 (8) ◽  
pp. 1911-1916 ◽  
Author(s):  
Anja Lührmann ◽  
Jürgen Thölke ◽  
Ingrid Behn ◽  
Jens Schumann ◽  
Gisa Tiegs ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Adp Ribosylation ◽  
Surface Molecules ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We show that the coumeromycin antibiotic novobiocin, a potent inhibitor of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-10 secretion in human peripheral blood mononuclear cells. It shares these cytokine-suppressing properties with other inhibitors of ADP ribosylation. We found that novobiocin prevents TNF-α production by inhibiting translation of the TNF-α mRNA. Elevated TNF-α levels in mice treated withd-galactosamine (GalN)-LPS or GalN-TNF were not reduced by novobiocin; however, the drug exhibited hepatoprotective properties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expression of surface molecules was not observed on T and B lymphocytes. Similar to other inhibitors of ADP ribosylation, novobiocin prevents LPS-induced phosphate labelling of γ-actins.

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