Schaeffer Evelyne, Flacher Vincent, Neuberg Patrick, Hoste Astrid, Brulefert Adrien, Fauny Jean-Daniel, Wagner Alain, Mueller Christopher G
Inhibition of dengue virus infection by mannoside glycolipid conjugates Journal Article
In: Antiviral Research, vol. 154, pp. 116–123, 2018, ISSN: 1872-9096.
Abstract | Links | BibTeX | Tags: Animals, Antiviral Agents, Cell Line, Cell Membrane, Chemistry, Chlorocebus aethiops, Dendritic Cells, Dengue, Dengue virus, development, Drug, Drug Discovery, Flavivirus, function, Fusion, Glycolipids, Health, Hep G2 Cells, Human, Humans, immunopathology, infection, inhibition, inhibitors, Inhibitory Concentration 50, lipid, Macrophages, Mannosides, Membrane, Serogroup, Skin, Team-Mueller, vaccine, Vaccines, Vero Cells, viral Infection, virus, Virus Replication
@article{schaeffer_inhibition_2018b,
title = {Inhibition of dengue virus infection by mannoside glycolipid conjugates},
author = {Evelyne Schaeffer and Vincent Flacher and Patrick Neuberg and Astrid Hoste and Adrien Brulefert and Jean-Daniel Fauny and Alain Wagner and Christopher G Mueller},
doi = {10.1016/j.antiviral.2018.04.005},
issn = {1872-9096},
year = {2018},
date = {2018-01-01},
journal = {Antiviral Research},
volume = {154},
pages = {116--123},
abstract = {Dengue virus (DENV), a mosquito-borne flavivirus, causes severe and potentially fatal symptoms in millions of infected individuals each year. Although dengue fever represents a major global public health problem, the vaccines or antiviral drugs proposed so far have not shown sufficient efficacy and safety, calling for new antiviral developments. Here we have shown that a mannoside glycolipid conjugate (MGC) bearing a trimannose head with a saturated lipid chain inhibited DENV productive infection. It showed remarkable cell promiscuity, being active in human skin dendritic cells, hepatoma cell lines and Vero cells, and was active against all four DENV serotypes, with an IC50 in the low micromolar range. Time-of-addition experiments and structure-activity analyses revealed the importance of the lipid chain to interfere with an early viral infection step. This, together with a correlation between antiviral activity and membrane polarization by the lipid moiety indicated that the inhibitor functions by blocking viral envelope fusion with the endosome membrane. These finding establish MGCs as a novel class of antivirals against the DENV.},
keywords = {Animals, Antiviral Agents, Cell Line, Cell Membrane, Chemistry, Chlorocebus aethiops, Dendritic Cells, Dengue, Dengue virus, development, Drug, Drug Discovery, Flavivirus, function, Fusion, Glycolipids, Health, Hep G2 Cells, Human, Humans, immunopathology, infection, inhibition, inhibitors, Inhibitory Concentration 50, lipid, Macrophages, Mannosides, Membrane, Serogroup, Skin, Team-Mueller, vaccine, Vaccines, Vero Cells, viral Infection, virus, Virus Replication},
pubstate = {published},
tppubtype = {article}
}
Muller Quentin, Beaudet Marie-Josée, Serres-Bérard Thiéry De, Bellenfant Sabrina, Flacher Vincent, Berthod François
Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells Journal Article
In: Acta Biomaterialia, vol. 82, pp. 93–101, 2018, ISSN: 1878-7568.
Abstract | Links | BibTeX | Tags: atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1
@article{muller_development_2018,
title = {Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells},
author = {Quentin Muller and Marie-Josée Beaudet and Thiéry De Serres-Bérard and Sabrina Bellenfant and Vincent Flacher and François Berthod},
doi = {10.1016/j.actbio.2018.10.011},
issn = {1878-7568},
year = {2018},
date = {2018-01-01},
journal = {Acta Biomaterialia},
volume = {82},
pages = {93--101},
abstract = {Cutaneous innervation is increasingly recognized as a major element of skin physiopathology through the neurogenic inflammation driven by neuropeptides that are sensed by endothelial cells and the immune system. To investigate this process in vitro, models of innervated tissue-engineered skin (TES) were developed, yet exclusively with murine sensory neurons extracted from dorsal root ganglions. In order to build a fully human model of innervated TES, we used induced pluripotent stem cells (iPSC) generated from human skin fibroblasts. Nearly 100% of the iPSC differentiated into sensory neurons were shown to express the neuronal markers BRN3A and β3-tubulin after 19 days of maturation. In addition, these cells were also positive to TRPV1 and neurofilament M, and some of them expressed Substance P, TrkA and TRPA1. When stimulated with molecules inducing neuropeptide release, iPSC-derived neurons released Substance P and CGRP, both in conventional monolayer culture and after seeding in a 3D fibroblast-populated collagen sponge model. Schwann cells, the essential partners of neurons for function and axonal migration, were also successfully differentiated from human iPSC as shown by their expression of the markers S100, GFAP, p75 and SOX10. When cultured for one additional month in the TES model, iPSC-derived neurons seeded at the bottom of the sponge formed a network of neurites spanning the whole TES up to the epidermis, but only when combined with mouse or iPSC-derived Schwann cells. This unique model of human innervated TES should be highly useful for the study of cutaneous neuroinflammation. STATEMENT OF SIGNIFICANCE: The purpose of this work was to develop in vitro an innovative fully human tissue-engineered skin enabling the investigation of the influence of cutaneous innervation on skin pathophysiology. To reach that aim, neurons were differentiated from human induced pluripotent stem cells (iPSCs) generated from normal human skin fibroblasts. This innervated tissue-engineered skin model will be the first one to show iPSC-derived neurons can be successfully used to build a 3D nerve network in vitro. Since innervation has been recently recognized to play a central role in many human skin diseases, such as psoriasis and atopic dermatitis, this construct promises to be at the forefront to model these diseases while using patient-derived cells.},
keywords = {atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1},
pubstate = {published},
tppubtype = {article}
}
Flacher Vincent, Neuberg Patrick, Point Floriane, Daubeuf François, Muller Quentin, Sigwalt David, Fauny Jean-Daniel, Remy Jean-Serge, Frossard Nelly, Wagner Alain, Mueller Christopher G, Schaeffer Evelyne
Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation Journal Article
In: ACS chemical biology, vol. 10, no. 12, pp. 2697–2705, 2015, ISSN: 1554-8937.
Abstract | Links | BibTeX | Tags: Activation, Animals, Anti-Inflammatory Agents, Carbohydrate Sequence, CD14, Cell Membrane, Cells, Chemistry, Cultured, cytokine, Dendritic Cells, development, disease, Glycolipids, Human, Humans, immunopathology, Inbred BALB C, inflammation, inhibition, lipid, lipopolysaccharide, Lipopolysaccharides, LPS, LUNG, Mannosides, Maturation, Membrane, Mice, monocyte, Monocytes, mouse, neutrophils, NF-kappaB, Pneumonia, Protein-Serine-Threonine Kinases, Receptor, secretion, signaling, Structure-Activity Relationship, Tail, Team-Mueller, TLR4, Toll-Like Receptor 4
@article{flacher_mannoside_2015b,
title = {Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation},
author = {Vincent Flacher and Patrick Neuberg and Floriane Point and François Daubeuf and Quentin Muller and David Sigwalt and Jean-Daniel Fauny and Jean-Serge Remy and Nelly Frossard and Alain Wagner and Christopher G Mueller and Evelyne Schaeffer},
doi = {10.1021/acschembio.5b00552},
issn = {1554-8937},
year = {2015},
date = {2015-12-01},
journal = {ACS chemical biology},
volume = {10},
number = {12},
pages = {2697--2705},
abstract = {Inhibition of excessive Toll-like receptor 4 (TLR4) signaling is a therapeutic approach pursued for many inflammatory diseases. We report that Mannoside Glycolipid Conjugates (MGCs) selectively blocked TLR4-mediated activation of human monocytes and monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS). They potently suppressed pro-inflammatory cytokine secretion and maturation of DCs exposed to LPS, leading to impaired T cell stimulation. MGCs did not interfere with LPS and could act in a delayed manner, hours after LPS stimulation. Their inhibitory action required both the sugar heads and the lipid chain, although the nature of the sugar and the structure of the lipid tail could be modified. They blocked early signaling events at the cell membrane, enhanced internalization of CD14 receptors, and prevented colocalization of CD14 and TLR4, thereby abolishing NF-κB nuclear translocation. When the best lead conjugate was tested in a mouse model of LPS-induced acute lung inflammation, it displayed an anti-inflammatory action by suppressing the recruitment of neutrophils. Thus, MGCs could serve as promising leads for the development of selective TLR4 antagonistic agents for inflammatory diseases.},
keywords = {Activation, Animals, Anti-Inflammatory Agents, Carbohydrate Sequence, CD14, Cell Membrane, Cells, Chemistry, Cultured, cytokine, Dendritic Cells, development, disease, Glycolipids, Human, Humans, immunopathology, Inbred BALB C, inflammation, inhibition, lipid, lipopolysaccharide, Lipopolysaccharides, LPS, LUNG, Mannosides, Maturation, Membrane, Mice, monocyte, Monocytes, mouse, neutrophils, NF-kappaB, Pneumonia, Protein-Serine-Threonine Kinases, Receptor, secretion, signaling, Structure-Activity Relationship, Tail, Team-Mueller, TLR4, Toll-Like Receptor 4},
pubstate = {published},
tppubtype = {article}
}
Mairhofer David G, Ortner Daniela, Tripp Christoph H, Schaffenrath Sandra, Fleming Viktor, Heger Lukas, Komenda Kerstin, Reider Daniela, Dudziak Diana, Chen Suzie, Becker Jürgen C, Flacher Vincent, Stoitzner Patrizia
Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model Journal Article
In: The Journal of Investigative Dermatology, vol. 135, no. 11, pp. 2785–2793, 2015, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity
@article{mairhofer_impaired_2015,
title = {Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model},
author = {David G Mairhofer and Daniela Ortner and Christoph H Tripp and Sandra Schaffenrath and Viktor Fleming and Lukas Heger and Kerstin Komenda and Daniela Reider and Diana Dudziak and Suzie Chen and Jürgen C Becker and Vincent Flacher and Patrizia Stoitzner},
doi = {10.1038/jid.2015.241},
issn = {1523-1747},
year = {2015},
date = {2015-11-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {11},
pages = {2785--2793},
abstract = {Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.},
keywords = {Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity},
pubstate = {published},
tppubtype = {article}
}
Schaeffer Evelyne, Flacher Vincent, Papageorgiou Vasiliki, Decossas Marion, Fauny Jean-Daniel, Krämer Melanie, Mueller Christopher G
Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4 Journal Article
In: The Journal of Investigative Dermatology, vol. 135, no. 7, pp. 1743–1751, 2015, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: Abdominal Wall, Activation, Adhesion, adhesion molecules, Antigen-Presenting Cells, arbovirus, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Cells, Chemistry, Confocal, Cultured, cytokine, Cytokines, cytology, Dendritic Cells, Dengue, Dengue virus, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, development, disease, Enzyme-Linked Immunosorbent Assay, Epidermal Cells, Epidermis, Human, Humans, ICAM-3, IL-4, Immunology, immunopathology, infection, Interleukin-4, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Macrophage, Macrophages, metabolism, Microscopy, pathogenicity, physiopathology, Receptor, Receptors, Scabies, Sensitivity and Specificity, Skin, Skin Diseases, SUBSETS, T CELL ACTIVATION, target, Team-Mueller, TNF ALPHA, Viral, viral Infection, Viral Load, virology, virus
@article{schaeffer_dermal_2015b,
title = {Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4},
author = {Evelyne Schaeffer and Vincent Flacher and Vasiliki Papageorgiou and Marion Decossas and Jean-Daniel Fauny and Melanie Krämer and Christopher G Mueller},
doi = {10.1038/jid.2014.525},
issn = {1523-1747},
year = {2015},
date = {2015-07-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {7},
pages = {1743--1751},
abstract = {Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.},
keywords = {Abdominal Wall, Activation, Adhesion, adhesion molecules, Antigen-Presenting Cells, arbovirus, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Cells, Chemistry, Confocal, Cultured, cytokine, Cytokines, cytology, Dendritic Cells, Dengue, Dengue virus, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, development, disease, Enzyme-Linked Immunosorbent Assay, Epidermal Cells, Epidermis, Human, Humans, ICAM-3, IL-4, Immunology, immunopathology, infection, Interleukin-4, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Macrophage, Macrophages, metabolism, Microscopy, pathogenicity, physiopathology, Receptor, Receptors, Scabies, Sensitivity and Specificity, Skin, Skin Diseases, SUBSETS, T CELL ACTIVATION, target, Team-Mueller, TNF ALPHA, Viral, viral Infection, Viral Load, virology, virus},
pubstate = {published},
tppubtype = {article}
}
Mueller Christopher G, Coles Mark Christopher
Emerging immune functions of non-hematopoietic stromal cells Journal Article
In: Frontiers in Immunology, vol. 5, pp. 437, 2014, ISSN: 1664-3224.
Links | BibTeX | Tags: development, immune cells, inflammation, Lymphoid Tissue, Stromal Cells, Team-Mueller
@article{mueller_emerging_2014,
title = {Emerging immune functions of non-hematopoietic stromal cells},
author = {Christopher G Mueller and Mark Christopher Coles},
doi = {10.3389/fimmu.2014.00437},
issn = {1664-3224},
year = {2014},
date = {2014-01-01},
journal = {Frontiers in Immunology},
volume = {5},
pages = {437},
keywords = {development, immune cells, inflammation, Lymphoid Tissue, Stromal Cells, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Hess E, Duheron V, Decossas M, Lezot F, Berdal A, Chea S, Golub R, Bosisio M R, Bridal S L, Choi Y, Yagita H, Mueller C G
RANKL induces organized lymph node growth by stromal cell proliferation Journal Article
In: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), pp. 1245–1254, 2012.
Abstract | Links | BibTeX | Tags: Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Proliferation, Chemokine CCL19, Chemokine CXCL13, chemokines, CXCL13, cytology, development, Growth, growth & development, Hair, hair follicle, Homeostasis, Human, Immune System, Immunization, ligand, LYMPH, LYMPH NODE, Lymph Nodes, Mice, mouse, physiology, plasticity, Proliferation, Protein, rank, RANK ligand, Regulation, Secondary, Stromal Cells, Team-Mueller, transgenic, VCAM1
@article{hess_rankl_2012,
title = {RANKL induces organized lymph node growth by stromal cell proliferation},
author = {E Hess and V Duheron and M Decossas and F Lezot and A Berdal and S Chea and R Golub and M R Bosisio and S L Bridal and Y Choi and H Yagita and C G Mueller},
doi = {10.4049/jimmunol.1101513},
year = {2012},
date = {2012-01-01},
journal = {Journal of Immunology},
volume = {188},
number = {1550-6606 (Electronic)},
pages = {1245--1254},
abstract = {RANK and its ligand RANKL play important roles in the development and regulation of the immune system. We show that mice transgenic for Rank in hair follicles display massive postnatal growth of skin-draining lymph nodes. The proportions of hematopoietic and nonhematopoietic stromal cells and their organization are maintained, with the exception of an increase in B cell follicles. The hematopoietic cells are not activated and respond to immunization by foreign Ag and adjuvant. We demonstrate that soluble RANKL is overproduced from the transgenic hair follicles and that its neutralization normalizes lymph node size, inclusive area, and numbers of B cell follicles. Reticular fibroblastic and vascular stromal cells, important for secondary lymphoid organ formation and organization, express RANK and undergo hyperproliferation, which is abrogated by RANKL neutralization. In addition, they express higher levels of CXCL13 and CCL19 chemokines, as well as MAdCAM-1 and VCAM-1 cell-adhesion molecules. These findings highlight the importance of tissue-derived cues for secondary lymphoid organ homeostasis and identify RANKL as a key molecule for controlling the plasticity of the immune system},
keywords = {Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Proliferation, Chemokine CCL19, Chemokine CXCL13, chemokines, CXCL13, cytology, development, Growth, growth & development, Hair, hair follicle, Homeostasis, Human, Immune System, Immunization, ligand, LYMPH, LYMPH NODE, Lymph Nodes, Mice, mouse, physiology, plasticity, Proliferation, Protein, rank, RANK ligand, Regulation, Secondary, Stromal Cells, Team-Mueller, transgenic, VCAM1},
pubstate = {published},
tppubtype = {article}
}
Durand Stéphanie H, Flacher Vincent, Roméas Annick, Carrouel Florence, Colomb Evelyne, Vincent Claude, Magloire Henry, Couble Marie-Lise, Bleicher Françoise, Staquet Marie-Jeanne, Lebecque Serge, Farges Jean-Christophe
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 176, no. 5, pp. 2880–2887, 2006, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation
@article{durand_lipoteichoic_2006,
title = {Lipoteichoic acid increases TLR and functional chemokine expression while reducing dentin formation in in vitro differentiated human odontoblasts},
author = {Stéphanie H Durand and Vincent Flacher and Annick Roméas and Florence Carrouel and Evelyne Colomb and Claude Vincent and Henry Magloire and Marie-Lise Couble and Françoise Bleicher and Marie-Jeanne Staquet and Serge Lebecque and Jean-Christophe Farges},
doi = {10.4049/jimmunol.176.5.2880},
issn = {0022-1767},
year = {2006},
date = {2006-03-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {176},
number = {5},
pages = {2880--2887},
abstract = {Gram-positive bacteria entering the dentinal tissue during the carious process are suspected to influence the immune response in human dental pulp. Odontoblasts situated at the pulp/dentin interface are the first cells encountered by these bacteria and therefore could play a crucial role in this response. In the present study, we found that in vitro-differentiated odontoblasts constitutively expressed the pattern recognition receptor TLR1-6 and 9 genes but not TLR7, 8, and 10. Furthermore, lipoteichoic acid (LTA), a wall component of Gram-positive bacteria, triggered the activation of the odontoblasts. LTA up-regulated the expression of its own receptor TLR2, as well as the production of several chemokines. In particular, an increased amount of CCL2 and CXCL10 was detected in supernatants from LTA-stimulated odontoblasts, and those supernatants augmented the migration of immature dendritic cells in vitro compared with controls. Clinical relevance of these observations came from immunohistochemical analysis showing that CCL2 was expressed in vivo by odontoblasts and blood vessels present under active carious lesions but not in healthy dental pulps. In contrast with this inflammatory response, gene expression of major dentin matrix components (type I collagen, dentin sialophosphoprotein) and TGF-beta1 was sharply down-regulated in odontoblasts by LTA. Taken together, these data suggest that odontoblasts activated through TLR2 by Gram-positive bacteria LTA are able to initiate an innate immune response by secreting chemokines that recruit immature dendritic cells while down-regulating their specialized functions of dentin matrix synthesis and mineralization.},
keywords = {Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
Heyman T., Agoutin B., Fix C., Dirheimer G., Keith G.
Yeast serine isoacceptor tRNAs: variations of their content as a function of growth conditions and primary structure of the minor tRNA(Ser)GCU Journal Article
In: FEBS Lett, vol. 347, no. 2-3, pp. 143-6, 1994, (0014-5793 Journal Article).
Abstract | BibTeX | Tags: &, Acid, Anticodon, Base, cerevisiae/*genetics/*growth, Conformation, Culture, Data, development, Fungal/*chemistry, Galactose, Hybridization, Media, Molecular, Nucleic, Probes, RNA, Saccharomyces, Sequence, Ser/analysis/*chemistry, Transfer, Transfer/*chemistry
@article{,
title = {Yeast serine isoacceptor tRNAs: variations of their content as a function of growth conditions and primary structure of the minor tRNA(Ser)GCU},
author = { T. Heyman and B. Agoutin and C. Fix and G. Dirheimer and G. Keith},
year = {1994},
date = {1994-01-01},
journal = {FEBS Lett},
volume = {347},
number = {2-3},
pages = {143-6},
abstract = {The primary structure of Saccharomyces cerevisiae tRNA(Ser)GCU is presented (EMBL database accession No. X74268 S. cerevisiae tRNA-Ser). In addition, quantitation of the relative amounts of serine isoaccepting tRNAs in yeast grown on different media showed that the minor tRNA(Ser)GCU decreased while the major tRNA(Ser)AGA increased as the growth rate and the cellular protein content increased. The minor species, tRNA(Ser)CGA and tRNA(Ser)UGA, were not separated by our gel system, however, taken together they appeared to vary in the same way as tRNA(Ser)GCU. These data suggest a growth rate dependence of yeast tRNAs similar to that previously described for E. coli tRNAs.},
note = {0014-5793
Journal Article},
keywords = {&, Acid, Anticodon, Base, cerevisiae/*genetics/*growth, Conformation, Culture, Data, development, Fungal/*chemistry, Galactose, Hybridization, Media, Molecular, Nucleic, Probes, RNA, Saccharomyces, Sequence, Ser/analysis/*chemistry, Transfer, Transfer/*chemistry},
pubstate = {published},
tppubtype = {article}
}
Moine H., Dahlberg A. E.
Mutations in helix 34 of Escherichia coli 16 S ribosomal RNA have multiple effects on ribosome function and synthesis Journal Article
In: J Mol Biol, vol. 243, no. 3, pp. 402-12, 1994, (0022-2836 Journal Article).
Abstract | BibTeX | Tags: *Mutation, *Nucleic, *Translation, &, 16S/*chemistry/genetics, Acid, Base, beta-Galactosidase/genetics, Codon, coli/*genetics/growth, Conformation, Data, development, Escherichia, Genetic, Gov't, Molecular, Non-U.S., P.H.S., Ribosomal, Ribosomes/*metabolism, RNA, Sequence, Support, Terminator, U.S.
@article{,
title = {Mutations in helix 34 of Escherichia coli 16 S ribosomal RNA have multiple effects on ribosome function and synthesis},
author = { H. Moine and A. E. Dahlberg},
year = {1994},
date = {1994-01-01},
journal = {J Mol Biol},
volume = {243},
number = {3},
pages = {402-12},
abstract = {Helix 34 of E. coli 16 S rRNA (1046 to 1067 and 1189 to 1211) has been proposed to participate directly in the termination of translation at UGA stop codons. We have constructed mutations in this helix in plasmid-encoded rDNA to explore the specific functional roles of the sequence UCAUCA (1199 to 1204) and a secondary structure also involving positions 1054 and 1057-1058. The rRNA mutations were analyzed for their effects on in vivo translational accuracy (stop codon readthrough and frameshifting) as well as growth rate, ribosome synthesis and incorporation into polysomes. Mutations at positions 1054, 1057, 1058, 1199 and 1200 had significant effects on translational accuracy, causing non-specific readthrough of all three stop codons as well as enhanced +1 and -1 frameshifting. Mutations at 1202 and 1203, however, had no effect. The incorporation of deleterious mutant subunits into 70 S ribosomes and polysomes was severely reduced and was associated with a slower growth rate and increased synthesis of host-encoded ribosomes. These data support the proposal that helix 34 is an essential component of the decoding center of the 30 S ribosomal subunit and is not restricted in function to UGA-codon specific termination.},
note = {0022-2836
Journal Article},
keywords = {*Mutation, *Nucleic, *Translation, &, 16S/*chemistry/genetics, Acid, Base, beta-Galactosidase/genetics, Codon, coli/*genetics/growth, Conformation, Data, development, Escherichia, Genetic, Gov't, Molecular, Non-U.S., P.H.S., Ribosomal, Ribosomes/*metabolism, RNA, Sequence, Support, Terminator, U.S.},
pubstate = {published},
tppubtype = {article}
}
Pochart P., Agoutin B., Fix C., Keith G., Heyman T.
A very poorly expressed tRNA(Ser) is highly concentrated together with replication primer initiator tRNA(Met) in the yeast Ty1 virus-like particles Journal Article
In: Nucleic Acids Res, vol. 21, no. 7, pp. 1517-21, 1993, (0305-1048 Journal Article).
Abstract | BibTeX | Tags: &, Acid, Base, cerevisiae/metabolism, Conformation, Data, development, DNA, Electrophoresis, Elements/*physiology, Gel, Met/metabolism, Molecular, Nucleic, Retroviridae/*growth, RNA, Saccharomyces, Sequence, Ser/*metabolism, Transfer, Transposable, Two-Dimensional, Viral/*metabolism
@article{,
title = {A very poorly expressed tRNA(Ser) is highly concentrated together with replication primer initiator tRNA(Met) in the yeast Ty1 virus-like particles},
author = { P. Pochart and B. Agoutin and C. Fix and G. Keith and T. Heyman},
year = {1993},
date = {1993-01-01},
journal = {Nucleic Acids Res},
volume = {21},
number = {7},
pages = {1517-21},
abstract = {The analysis of the tRNAs associated to the virus-like particles produced by the Ty1 element revealed the specific packaging of three major tRNA species, in about equal amounts: the replication primer initiator tRNA(Met), the tRNA(Ser)AGA and a tRNA undetected until now as an expressed species in yeast. The latter tRNA is coded by the already described tDNA(Ser)GCT. This tRNA is enriched more than 150 fold in the particles as compared to its content in total cellular tRNA where it represents less than 0.1% (initiator tRNA(Met) and tRNA(Ser)AGA being 11 and 4 fold enriched respectively). This tRNA is the only species coded by the tDNA(Ser)GCT gene which is found in three copies per genome since no other corresponding expressed tRNA could be detected. This gene is thus very poorly expressed. The high concentration of tRNA(Ser)GCU in the particles compared to its very low cellular content led us to consider its possible implication in Ty specific processes.},
note = {0305-1048
Journal Article},
keywords = {&, Acid, Base, cerevisiae/metabolism, Conformation, Data, development, DNA, Electrophoresis, Elements/*physiology, Gel, Met/metabolism, Molecular, Nucleic, Retroviridae/*growth, RNA, Saccharomyces, Sequence, Ser/*metabolism, Transfer, Transposable, Two-Dimensional, Viral/*metabolism},
pubstate = {published},
tppubtype = {article}
}