Imagerie

@article{schaeffer_inhibition_2018,

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 = {Cell Membrane, Dendritic Cells, Dengue virus, I2CT, Imagerie, inhibitors, Macrophages, Skin, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@article{baron_parental_2013,

title = {Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections},

author = {Olga Lucia Baron and Pieter van West and Benoit Industri and Michel Ponchet and Géraldine Dubreuil and Benjamin Gourbal and Jean-Marc Reichhart and Christine Coustau},

doi = {10.1371/journal.ppat.1003792},

issn = {1553-7374},

year  = {2013},

date = {2013-01-01},

journal = {PLoS Pathog.},

volume = {9},

number = {12},

pages = {e1003792},

abstract = {Vertebrate females transfer antibodies via the placenta, colostrum and milk or via the egg yolk to protect their immunologically immature offspring against pathogens. This evolutionarily important transfer of immunity is poorly documented in invertebrates and basic questions remain regarding the nature and extent of parental protection of offspring. In this study, we show that a lipopolysaccharide binding protein/bactericidal permeability increasing protein family member from the invertebrate Biomphalaria glabrata (BgLBP/BPI1) is massively loaded into the eggs of this freshwater snail. Native and recombinant proteins displayed conserved LPS-binding, antibacterial and membrane permeabilizing activities. A broad screening of various pathogens revealed a previously unknown biocidal activity of the protein against pathogenic water molds (oomycetes), which is conserved in human BPI. RNAi-dependent silencing of LBP/BPI in the parent snails resulted in a significant reduction of reproductive success and extensive death of eggs through oomycete infections. This work provides the first functional evidence that a LBP/BPI is involved in the parental immune protection of invertebrate offspring and reveals a novel and conserved biocidal activity for LBP/BPI family members.},

keywords = {Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Biomphalaria, Blood Proteins, Carrier Proteins, Cell Membrane, Cell Membrane Permeability, Cloning, Escherichia coli, Female, Immunity, infection, M3i, Maternally-Acquired, Membrane Glycoproteins, Microbial Sensitivity Tests, Molecular, Oomycetes, Recombinant Proteins, reichhart, Zygote},

pubstate = {published},

tppubtype = {article}

}

@article{lacerda_translocation_2012,

title = {Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes},

author = {Lara Lacerda and Julie Russier and Giorgia Pastorin and Antonia M Herrero and Enrica Venturelli and Hélène Dumortier and Khuloud T Al-Jamal and Maurizio Prato and Kostas Kostarelos and Alberto Bianco},

doi = {10.1016/j.biomaterials.2012.01.024},

issn = {1878-5905},

year  = {2012},

date = {2012-01-01},

journal = {Biomaterials},

volume = {33},

number = {11},

pages = {3334--3343},

abstract = {Understanding the mechanisms responsible for carbon nanotube (CNT) internalisation into live cells is considered critical both from a fundamental point of view and for further engineering of CNT-based delivery systems to intracellular targets. While several studies are focused on the development of such CNT-based delivery systems, attempts to systematically elucidate the cellular uptake mechanisms of CNTs are still rather limited. The aim of the present study is to evaluate the cellular internalisation of chemically functionalised multi-walled carbon nanotubes (f-MWCNTs) in the presence of different well-known cellular uptake inhibitors. Our data reveal how f-MWCNTs are able to translocate across cell membranes of both phagocytic and non-phagocytic cell lines. We have evidenced that at least 30-50% of f-MWCNTs are taken up by cells through an energy-independent mechanism. This characteristic makes nanotubes loaded with therapeutic or diagnostic cargos extremely interesting as the release of active molecules directly into the cytoplasm increase their biological activity and therapeutic efficacy.},

keywords = {Animals, carbon, Cell Line, Cell Membrane, Dumortier, I2CT, Macrophages, Mice, Nanotubes, Phagocytosis, Team-Bianco, Team-Dumortier},

pubstate = {published},

tppubtype = {article}

}

@article{al-jamal_cellular_2011,

title = {Cellular uptake mechanisms of functionalised multi-walled carbon nanotubes by 3D electron tomography imaging},

author = {Khuloud T Al-Jamal and Hannah Nerl and Karin H Müller and Hanene Ali-Boucetta and Shouping Li and Peter D Haynes and Joerg R Jinschek and Maurizio Prato and Alberto Bianco and Kostas Kostarelos and Alexandra E Porter},

doi = {10.1039/c1nr10080g},

issn = {2040-3372},

year  = {2011},

date = {2011-06-01},

journal = {Nanoscale},

volume = {3},

number = {6},

pages = {2627--2635},

abstract = {Carbon nanotubes (CNTs) are being investigated for a variety of biomedical applications. Despite numerous studies, the pathways by which carbon nanotubes enter cells and their subsequent intracellular trafficking and distribution remain poorly determined. Here, we use 3-D electron tomography techniques that offer optimum enhancement of contrast between carbon nanotubes and the plasma membrane to investigate the mechanisms involved in the cellular uptake of shortened, functionalised multi-walled carbon nanotubes (MWNT-NH(3)(+)). Both human lung epithelial (A549) cells, that are almost incapable of phagocytosis and primary macrophages, capable of extremely efficient phagocytosis, were used. We observed that MWNT-NH(3)(+) were internalised in both phagocytic and non-phagocytic cells by any one of three mechanisms: (a) individually via membrane wrapping; (b) individually by direct membrane translocation; and (c) in clusters within vesicular compartments. At early time points following intracellular translocation, we noticed accumulation of nanotube material within various intracellular compartments, while a long-term (14-day) study using primary human macrophages revealed that MWNT-NH(3)(+) were able to escape vesicular (phagosome) entrapment by translocating directly into the cytoplasm.},

keywords = {carbon, Cell Line, Cell Membrane, Cytoplasm, Electron Microscope Tomography, Humans, I2CT, imaging, Macrophages, Nanotubes, Phagocytosis, Phagosomes, Team-Bianco, Three-Dimensional, tumor},

pubstate = {published},

tppubtype = {article}

}

@article{serag_trafficking_2011,

title = {Trafficking and subcellular localization of multiwalled carbon nanotubes in plant cells},

author = {Maged F Serag and Noritada Kaji and Claire Gaillard and Yukihiro Okamoto and Kazuyoshi Terasaka and Mohammad Jabasini and Manabu Tokeshi and Hajime Mizukami and Alberto Bianco and Yoshinobu Baba},

doi = {10.1021/nn102344t},

issn = {1936-086X},

year  = {2011},

date = {2011-01-01},

journal = {ACS nano},

volume = {5},

number = {1},

pages = {493--499},

abstract = {Major barriers to delivery of biomolecules are crossing the cellular membranes and achieving a high cytoplasmic concentration by circumventing entrapment into endosomes and other lytic organelles. Motivated by such aim, we have investigated the capability of multiwalled carbon nanotubes (MWCNTs) to penetrate the cell membrane of plant protoplasts (plant cells made devoid of their cell walls via enzymatic treatment) and studied their internalization mechanism via confocal imaging and TEM techniques. Our results indentified an endosome-escaping uptake mode of MWCNTs by plant protoplasts. Moreover, short MWCNTs (textbackslashtextless100 nm) were observed to target specific cellular substructures including the nucleus, plastids, and vacuoles. These findings are expected to have a significant impact on plant cell biology and transformation technologies.},

keywords = {Biological Transport, carbon, Catharanthus, Cell Membrane, Endosomes, I2CT, Intracellular Space, Nanotubes, Protoplasts, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{benincasa_antifungal_2011,

title = {Antifungal activity of amphotericin B conjugated to carbon nanotubes},

author = {Monica Benincasa and Sabrina Pacor and Wei Wu and Maurizio Prato and Alberto Bianco and Renato Gennaro},

doi = {10.1021/nn1023522},

issn = {1936-086X},

year  = {2011},

date = {2011-01-01},

journal = {ACS nano},

volume = {5},

number = {1},

pages = {199--208},

abstract = {Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.},

keywords = {Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{kostarelos_cellular_2007,

title = {Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type},

author = {Kostas Kostarelos and Lara Lacerda and Giorgia Pastorin and Wei Wu and Sébastien Wieckowski and Jacqueline Luangsivilay and Sylvie Godefroy and Davide Pantarotto and Jean-Paul Briand and Sylviane Muller and Maurizio Prato and Alberto Bianco},

doi = {10.1038/nnano.2006.209},

issn = {1748-3395},

year  = {2007},

date = {2007-02-01},

journal = {Nature Nanotechnology},

volume = {2},

number = {2},

pages = {108--113},

keywords = {Animals, carbon, Cell Membrane, Cells, Cultured, Diffusion, Humans, I2CT, Nanotubes, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{chen_weckle_2006,

title = {Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo},

author = {Li-Ying Chen and Juinn-Chin Wang and Yann Hyvert and Hui-Ping Lin and Norbert Perrimon and Jean-Luc Imler and Jui-Chou Hsu},

doi = {10.1016/j.cub.2006.05.050},

issn = {0960-9822},

year  = {2006},

date = {2006-06-01},

journal = {Current biology: CB},

volume = {16},

number = {12},

pages = {1183--1193},

abstract = {BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.},

keywords = {Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers},

pubstate = {published},

tppubtype = {article}

}

@article{pantarotto_translocation_2004,

title = {Translocation of bioactive peptides across cell membranes by carbon nanotubes},

author = {Davide Pantarotto and Jean-Paul Briand and Maurizio Prato and Alberto Bianco},

doi = {10.1039/b311254c},

issn = {1359-7345},

year  = {2004},

date = {2004-01-01},

journal = {Chemical Communications (Cambridge, England)},

number = {1},

pages = {16--17},

abstract = {Functionalised carbon nanotubes are able to cross the cell membrane and to accumulate in the cytoplasm or reach the nucleus without being toxic for the cell up to 10 [micro sign]M.},

keywords = {3T3 Cells, Animals, carbon, Cell Membrane, Confocal, Flow Cytometry, fluorescence, I2CT, Mice, Microscopy, Nanotubes, Particle Size, Peptides, Protein Transport, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{nisole_anti-hiv_1999,

title = {The anti-HIV pseudopeptide HB-19 forms a complex with the cell-surface-expressed nucleolin independent of heparan sulfate proteoglycans},

author = {S Nisole and B Krust and C Callebaut and G Guichard and S Muller and J P Briand and A G Hovanessian},

doi = {10.1074/jbc.274.39.27875},

issn = {0021-9258},

year  = {1999},

date = {1999-09-01},

journal = {The Journal of Biological Chemistry},

volume = {274},

number = {39},

pages = {27875--27884},

abstract = {The HB-19 pseudopeptide 5[Kpsi(CH(2)N)PR]-TASP, psi(CH(2)N) for reduced peptide bond, is a specific inhibitor of human immunodeficiency virus (HIV) infection in different CD4(+) cell lines and in primary T-lymphocytes and macrophages. Here, by using an experimental CD4(+) cell model to monitor HIV entry and infection, we demonstrate that HB-19 binds the cell surface and inhibits attachment of HIV particles to permissive cells. At concentrations that inhibit HIV attachment, HB-19 binds cells irreversibly, becomes complexed with the cell-surface-expressed nucleolin, and eventually results in its degradation. Accordingly, by confocal immunofluorescence microscopy, we demonstrate the drastic reduction of the cell-surface-expressed nucleolin following treatment of cells with HB-19. HIV particles can prevent the binding of HB-19 to cells and inhibit complex formation with nucleolin. Such a competition between viral particles and HB-19 is consistent with the implication of nucleolin in the process of HIV attachment to target cells. We show that another inhibitor of HIV infection, the fibroblast growth factor-2 (FGF-2) that uses cell-surface-expressed heparan sulfate proteoglycans as low affinity receptors, binds cells and blocks attachment of HIV to permissive cells. FGF-2 does not prevent the binding of HB-19 to cells and to nucleolin, and similarly HB-19 has no apparent effect on the binding of FGF-2 to the cell surface. The lack of competition between these two anti-HIV agents rules out the potential involvement of heparan sulfate proteoglycans in the mechanism of anti-HIV effect of HB-19, thus pointing out that nucleolin is its main target.},

keywords = {Anti-HIV Agents, Binding Sites, CD4-Positive T-Lymphocytes, Cell Line, Cell Membrane, Confocal, Fibroblast Growth Factor 2, Flow Cytometry, Heparan Sulfate Proteoglycans, HIV-1, Humans, Microscopy, Oligopeptides, Peptides, Phospholipid Ethers, Phosphoproteins, Proteins, RNA-Binding Proteins},

pubstate = {published},

tppubtype = {article}

}

@article{zachary_new_1972,

title = {A new type of blood cell (the thrombocytoid) in Calliphora erythrocephala},

author = {Daniel Zachary and Jules A Hoffmann and A Porte},

year  = {1972},

date = {1972-07-01},

journal = {C.R. Hebd. Seances Acad. Sci., Ser. D, Sci. Nat.},

volume = {275},

number = {3},

pages = {393--395},

keywords = {Animals, Blood Cells, Blood Platelets, Cell Membrane, Cell Nucleus, Cytoplasm, Diptera, Electron, Hemolymph, hoffmann, M3i, Microscopy, Phase-Contrast},

pubstate = {published},

tppubtype = {article}

}