scholarly journals AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN

2007 ◽  
Vol 51 (7) ◽  
pp. 2313-2323 ◽  
Author(s):  
Diego Serrano-Gómez ◽  
Rocío T. Martínez-Nuñez ◽  
Elena Sierra-Filardi ◽  
Nuria Izquierdo ◽  
María Colmenares ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Molecular Mechanisms ◽  
Human Monocyte ◽  
Mannose Receptor ◽  
Receptor Expression ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Pathogen Recognition ◽  
Gp120 Protein ◽  
Human Dendritic Cells

ABSTRACT AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and 1D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.

scholarly journals DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells

2002 ◽  
Vol 197 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Ludovic Tailleux ◽  
Olivier Schwartz ◽  
Jean-Louis Herrmann ◽  
Elisabeth Pivert ◽  
Mary Jackson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Mannose Receptor ◽  
Intercellular Adhesion Molecule ◽  
Minor Role ◽  
Hla Dr ◽  
A Minor ◽  
Human Dendritic Cells

Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mϕs), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis–derived material was detected in CD14−HLA-DR+DC-SIGN+ cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN–mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity.

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 Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 617 ◽  
Author(s):  
Helen Freyberger ◽  
Yunxiu He ◽  
Amanda Roth ◽  
Mikeljon Nikolich ◽  
Andrey Filippov
Keyword(s):  
Staphylococcus Aureus ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Adaptive Immune Response ◽  
Human Monocyte ◽  
Activation Markers ◽  
Mhc I ◽  
Adaptive Immune ◽  
Human Dendritic Cells

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.

scholarly journals CRISPR-based functional genomics in human dendritic cells

2020 ◽  
Author(s):  
Marco Jost ◽  
Amy N. Jacobson ◽  
Jeffrey A. Hussmann ◽  
Giana Cirolia ◽  
Michael A. Fischbach ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Genome Editing ◽  
Individual Variation ◽  
Human Microbiome ◽  
Human Monocyte ◽  
Genetic Screens ◽  
Mucosal Surfaces ◽  
Immune Phenotypes ◽  
Human Dendritic Cells

AbstractDendritic cells (DCs) regulate processes ranging from antitumor and antiviral immunity to host-microbe communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses. Here, we develop a CRISPR/Cas9 genome editing method for human monocyte-derived DCs (moDCs) that mediates knockouts with a median efficiency of >93% across >300 genes. Using this method, we perform genetic screens in moDCs, identifying mechanisms by which DCs tune responses to lipopolysaccharides from the human microbiome. In addition, we reveal donor-specific responses to lipopolysaccharides, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify genes that control this specificity, highlighting the potential of our method to pinpoint determinants of inter-individual variation in immune responses. Our work sets the stage for a systematic dissection of the immune signaling at the host-microbiome interface and for targeted engineering of DCs for neoantigen vaccination.

scholarly journals Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production

1997 ◽  
Vol 186 (9) ◽  
pp. 1603-1608 ◽  
Author(s):  
Claudia Rieser ◽  
Günther Böck ◽  
Helmut Klocker ◽  
Georg Bartsch ◽  
Martin Thurnher
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Prostaglandin E2 ◽  
Tumor Necrosis ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Tnf Α ◽  
Human Dendritic Cells ◽  
Necrosis Factor

Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-α to induce high levels of IL-12 production by DCs. Addition of TNF-α in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-α efficiently silenced mannose receptor–mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-α were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.

scholarly journals Interaction of Monocyte-Derived Dendritic Cells with Ara h 2 from Raw and Roasted Peanuts

Foods ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 863 ◽  
Author(s):  
Natalija Novak ◽  
Soheila J. Maleki ◽  
Carmen Cuadrado ◽  
Jesus F. Crespo ◽  
Beatriz Cabanillas
Keyword(s):  
Dendritic Cells ◽  
Human Monocyte ◽  
Mannose Receptor ◽  
Allergic Reactions ◽  
Ara H 2 ◽  
Allergenic Potential ◽  
Sensitization Phase ◽  
Mannose Receptors ◽  
Dose Dependent

Ara h 2 is a relevant peanut allergen linked to severe allergic reactions. The interaction of Ara h 2 with components of the sensitization phase of food allergy (e.g., dendritic cells) has not been investigated, and could be key to understanding the allergenic potential of this allergen. In this study, we aimed to analyze such interactions and the possible mechanism involved. Ara h 2 was purified from two forms of peanut, raw and roasted, and labeled with a fluorescent dye. Human monocyte-derived dendritic cells (MDDCs) were obtained, and experiments of Ara h 2 internalization by MDDCs were carried out. The role of the mannose receptor in the internalization of Ara h 2 from raw and roasted peanuts was also investigated. Results showed that Ara h 2 internalization by MDDCs was both time and dose dependent. Mannose receptors in MDDCs had a greater implication in the internalization of Ara h 2 from roasted peanuts. However, this receptor was also important in the internalization of Ara h 2 from raw peanuts, as opposed to other allergens such as raw Ara h 3.

Vascular Protective Effects of Xanthotoxin and Its Action Mechanism in Rat Aorta and Human Vascular Endothelial Cells

2020 ◽  
Vol 57 (6) ◽  
pp. 313-324
Author(s):  
Li-Hua Cao ◽  
Ho Sub Lee ◽  
Zhe-Shan Quan ◽  
Yun Jung Lee ◽  
Yu Jin
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner

<b><i>Objective:</i></b> Xanthotoxin (XAT) is a linear furanocoumarin mainly extracted from the plants <i>Ammi majus</i> L. XAT has been reported the apoptosis of tumor cells, anti-convulsant, neuroprotective effect, antioxidative activity, and vasorelaxant effects. This study aimed to investigate the vascular protective effects and underlying molecular mechanisms of XAT. <b><i>Methods:</i></b> XAT’s activity was studied in rat thoracic aortas, isolated with aortic rings, and human umbilical vein endothelial cells (HUVECs). <b><i>Results:</i></b> XAT induced endothelium-dependent vasodilation in a concentration-dependent manner in the isolated rat thoracic aortas. Removal of endothelium or pretreatment of aortic rings with L-NAME, 1<i>H</i>-[1,2,4]-oxadiazolo-[4,3-<i>a</i>]-quinoxalin-1-one, and wortmannin significantly inhibited XAT-induced relaxation. In addition, treatment with thapsigargin, 2-aminoethyl diphenylborinate, Gd<sup>3+</sup>, and 4-aminopyridine markedly attenuated the XAT-induced vasorelaxation. XAT increased nitric oxide production and Akt- endothelial NOS (eNOS) phosphorylation in HUVECs. Moreover, XAT attenuated the expression of TNF-α-induced cell adhesion molecules such as intercellular adhesion molecule, vascular cell adhesion molecule-1, and E-selectin. However, this effect was attenuated by the eNOS inhibitors L-NAME and asymmetric dimethylarginine. <b><i>Conclusions:</i></b> This study suggests that XAT induces vasorelaxation through the Akt-eNOS-cGMP pathway by activating the K<sub>V</sub> channel and inhibiting the L-type Ca<sup>2+</sup> channel. Furthermore, XAT exerts an inhibitory effect on vascular inflammation, which is correlated with the observed vascular protective effects.

HIV gp120 receptors on human dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2482-2488 ◽  
Author(s):  
Stuart G. Turville ◽  
Jim Arthos ◽  
Kelli Mac Donald ◽  
Garry Lynch ◽  
Hassan Naif ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Ex Vivo ◽  
Mannose Receptor ◽  
Lectin Receptor ◽  
Immunodeficiency Virus ◽  
Processing Pathways ◽  
Human Dendritic Cells ◽  
Hiv Gp120 ◽  
Hiv Envelope ◽  
Transfer Mechanisms

Abstract Dendritic cells (DCs) are important targets for human immunodeficiency virus (HIV) because of their roles during transmission and also maintenance of immune competence. Furthermore, DCs are a key cell in the development of HIV vaccines. In both these settings the mechanism of binding of the HIV envelope protein gp120 to DCs is of importance. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte-derived DCs (MDDCs) rather than CD4. In this study a novel biotinylated gp120 assay was used to determine whether CLR or CD4 were predominant receptors on MDDCs and ex vivo blood DCs. CLR bound more than 80% of gp120 on MDDCs, with residual binding attributable to CD4, reconfirming that CLRs were the major receptors for gp120 on MDDCs. However, in contrast to recent reports, gp120 binding to at least 3 CLRs was observed: DC-SIGN, mannose receptor, and unidentified trypsin resistant CLR(s). In marked contrast, freshly isolated and cultured CD11c+ve and CD11c−ve blood DCs only bound gp120 via CD4. In view of these marked differences between MDDCs and blood DCs, HIV capture by DCs and transfer mechanisms to T cells as well as potential antigenic processing pathways will need to be determined for each DC phenotype.

The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells

1997 ◽  
Vol 27 (9) ◽  
pp. 2417-2425 ◽  
Author(s):  
Anneke J. Engering ◽  
Marina Cella ◽  
Donna Fluitsma ◽  
Manfred Brockhaus ◽  
Elizabeth C. M. Hoefsmit ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
High Capacity ◽  
Antigen Receptor ◽  
Mannose Receptor ◽  
Human Dendritic Cells ◽  
Broad Specificity
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