Publications
2018
Sawaf Matthieu, Fauny Jean-Daniel, Felten Renaud, Sagez Flora, Gottenberg Jacques-Eric, Dumortier Hélène, Monneaux Fanny
Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells Journal Article
In: JCI insight, vol. 3, no. 13, 2018, ISSN: 2379-3708.
Abstract | Links | BibTeX | Tags: 80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult
@article{sawaf_defective_2018,
title = {Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells},
author = {Matthieu Sawaf and Jean-Daniel Fauny and Renaud Felten and Flora Sagez and Jacques-Eric Gottenberg and Hélène Dumortier and Fanny Monneaux},
doi = {10.1172/jci.insight.99711},
issn = {2379-3708},
year = {2018},
date = {2018-01-01},
journal = {JCI insight},
volume = {3},
number = {13},
abstract = {Coinhibitory receptors play an important role in the prevention of autoimmune diseases, such as systemic lupus erythematosus (SLE), by limiting T cell activation. B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. The role of BTLA in the pathogenesis of autoimmune diseases in humans and, more specifically, in SLE is largely unknown. We investigated BTLA expression on various T cell subsets, and we did not observe significant variations of BTLA expression between lupus patients and healthy controls. However, the enhancement of BTLA expression after activation was significantly lower in SLE patients compared with that in healthy controls. Furthermore, we found an impaired capacity of BTLA to inhibit T cell activation in SLE due to a poor BTLA recruitment to the immunological synapse following T cell stimulation. Finally, we demonstrated that defective BTLA function can be corrected by restoring intracellular trafficking and by normalizing the lipid metabolism in lupus CD4+ T cells. Collectively, our results evidence that the BTLA signaling pathway is altered in SLE T cells and highlight the potential of targeting this pathway for the development of new therapeutic strategies in lupus.},
keywords = {80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult},
pubstate = {published},
tppubtype = {article}
}
2017
Nehmar Ramzi, Alsaleh Ghada, Voisin Benjamin, Flacher Vincent, Mariotte Alexandre, Saferding Victoria, Puchner Antonia, Niederreiter Birgit, Vandamme Thierry, Schabbauer Gernot, Kastner Philippe, Chan Susan, Kirstetter Peggy, Holcmann Martin, Mueller Christopher, Sibilia Jean, Bahram Seiamak, Blüml Stephan, Georgel Philippe
Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis Journal Article
In: Arthritis & Rheumatology (Hoboken, N.J.), vol. 69, no. 11, pp. 2124–2135, 2017, ISSN: 2326-5205.
Abstract | Links | BibTeX | Tags: Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha
@article{nehmar_therapeutic_2017,
title = {Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis},
author = {Ramzi Nehmar and Ghada Alsaleh and Benjamin Voisin and Vincent Flacher and Alexandre Mariotte and Victoria Saferding and Antonia Puchner and Birgit Niederreiter and Thierry Vandamme and Gernot Schabbauer and Philippe Kastner and Susan Chan and Peggy Kirstetter and Martin Holcmann and Christopher Mueller and Jean Sibilia and Seiamak Bahram and Stephan Blüml and Philippe Georgel},
doi = {10.1002/art.40225},
issn = {2326-5205},
year = {2017},
date = {2017-01-01},
journal = {Arthritis & Rheumatology (Hoboken, N.J.)},
volume = {69},
number = {11},
pages = {2124--2135},
abstract = {OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage.
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.},
keywords = {Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.
2015
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}
}
2013
Quintin Jessica, Asmar Joelle, Matskevich Alexey A, Lafarge Marie-Céline, Ferrandon Dominique
The Drosophila Toll pathway controls but does not clear Candida glabrata infections Journal Article
In: J. Immunol., vol. 190, no. 6, pp. 2818–2827, 2013, ISSN: 1550-6606.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Animal, Animals, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, ferrandon, Immunologic, M3i, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence
@article{quintin_drosophila_2013b,
title = {The Drosophila Toll pathway controls but does not clear Candida glabrata infections},
author = {Jessica Quintin and Joelle Asmar and Alexey A Matskevich and Marie-Céline Lafarge and Dominique Ferrandon},
doi = {10.4049/jimmunol.1201861},
issn = {1550-6606},
year = {2013},
date = {2013-03-01},
journal = {J. Immunol.},
volume = {190},
number = {6},
pages = {2818--2827},
abstract = {The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host.},
keywords = {Adaptor Proteins, Animal, Animals, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, ferrandon, Immunologic, M3i, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence},
pubstate = {published},
tppubtype = {article}
}
Ayyaz Arshad, Giammarinaro Philippe, Liégeois Samuel, Lestradet Matthieu, Ferrandon Dominique
In: Immunobiology, vol. 218, no. 4, pp. 635–644, 2013, ISSN: 1878-3279.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors
@article{ayyaz_negative_2013b,
title = {A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus},
author = {Arshad Ayyaz and Philippe Giammarinaro and Samuel Liégeois and Matthieu Lestradet and Dominique Ferrandon},
doi = {10.1016/j.imbio.2012.07.027},
issn = {1878-3279},
year = {2013},
date = {2013-01-01},
journal = {Immunobiology},
volume = {218},
number = {4},
pages = {635--644},
abstract = {Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development.},
keywords = {Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
2012
Thomann Jean-Sébastien, Monneaux Fanny, Creusat Gaëlle, Spanedda Maria Vittoria, Heurtault Béatrice, Habermacher Chloé, Schuber Francis, Bourel-Bonnet Line, Frisch Benoît
Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties Journal Article
In: European Journal of Medicinal Chemistry, vol. 51, pp. 174–183, 2012, ISSN: 1768-3254.
Abstract | Links | BibTeX | Tags: Adjuvants, Animals, Cell Line, Chemistry Techniques, Female, Galactose, Glycolipids, Humans, I2CT, Immunologic, ligands, Mice, Monneaux, Structure-Activity Relationship, Synthetic, Team-Dumortier, Toll-Like Receptor 2
@article{thomann_novel_2012,
title = {Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties},
author = {Jean-Sébastien Thomann and Fanny Monneaux and Gaëlle Creusat and Maria Vittoria Spanedda and Béatrice Heurtault and Chloé Habermacher and Francis Schuber and Line Bourel-Bonnet and Benoît Frisch},
doi = {10.1016/j.ejmech.2012.02.039},
issn = {1768-3254},
year = {2012},
date = {2012-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {51},
pages = {174--183},
abstract = {A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratiotextgreater9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships.},
keywords = {Adjuvants, Animals, Cell Line, Chemistry Techniques, Female, Galactose, Glycolipids, Humans, I2CT, Immunologic, ligands, Mice, Monneaux, Structure-Activity Relationship, Synthetic, Team-Dumortier, Toll-Like Receptor 2},
pubstate = {published},
tppubtype = {article}
}
2011
Banchet-Cadeddu Aline, Hénon Eric, Dauchez Manuel, Renault Jean-Hugues, Monneaux Fanny, Haudrechy Arnaud
The stimulating adventure of KRN 7000 Journal Article
In: Organic & Biomolecular Chemistry, vol. 9, no. 9, pp. 3080–3104, 2011, ISSN: 1477-0539.
Abstract | Links | BibTeX | Tags: Adjuvants, Animals, Antigen, Antigens, CD1d, Galactosylceramides, Helper-Inducer, Humans, I2CT, Immunologic, Monneaux, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier
@article{banchet-cadeddu_stimulating_2011,
title = {The stimulating adventure of KRN 7000},
author = {Aline Banchet-Cadeddu and Eric Hénon and Manuel Dauchez and Jean-Hugues Renault and Fanny Monneaux and Arnaud Haudrechy},
doi = {10.1039/c0ob00975j},
issn = {1477-0539},
year = {2011},
date = {2011-01-01},
journal = {Organic & Biomolecular Chemistry},
volume = {9},
number = {9},
pages = {3080--3104},
abstract = {Associated with the CD1d protein, KRN 7000, a potent synthetic α-galactosylceramide, is known to activate the invariant NKT immune cells. This stimulation then leads to the production of different cytokines modulating a T(H)1/T(H)2 immune response balance involved in protection against several pathologies such as autoimmune diseases and cancers. Various efforts have been made toward the synthesis of simple and more functionalized analogues in order to selectively induce T(H)1 or T(H)2-type cytokine production. Since the discovery of KRN 7000, structure-activity relationships, crystallographic and modelling studies have pointed to the potential of several GalCer analogues in term of selective bioactivity, and have highlighted interesting elements in order to better understand the recognition and activation mechanisms of immune iNKT cells. By presenting an up-to-date library of analogues, collecting recent breakthroughs done in crystallography and molecular modelling, and relating them to the available biological results, we hope that this review will highlight and help the scientific community in their KRN research.},
keywords = {Adjuvants, Animals, Antigen, Antigens, CD1d, Galactosylceramides, Helper-Inducer, Humans, I2CT, Immunologic, Monneaux, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2006
Chen Li-Ying, Wang Juinn-Chin, Hyvert Yann, Lin Hui-Ping, Perrimon Norbert, Imler Jean-Luc, Hsu Jui-Chou
Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo Journal Article
In: Current biology: CB, vol. 16, no. 12, pp. 1183–1193, 2006, ISSN: 0960-9822.
Abstract | Links | BibTeX | Tags: 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
@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}
}
Marmey B, Boix C, Barbaroux J B, Dieu-Nosjean M C, Diebold J, Audouin J, Fridman W H, Mueller C G, Molina T J
CD14 and CD169 expression in human lymph nodes and spleen: specific expansion of CD14+C Journal Article
In: Hum.Pathol., vol. 37, no. 0046-8177 (Print), pp. 68–77, 2006.
Abstract | BibTeX | Tags: Adhesion, Antigen, Antigens, B-Cell, Biological, CD14, Cell Differentiation, CELL SEPARATION, Dendritic Cells, Differentiation, Diffuse, Direct, Expression, Flow Cytometry, Fluorescent Antibody Technique, Gene, GLYCOPROTEIN, Glycoproteins, granulocyte/macrophage-colony, Human, Humans, Immunoenzyme Techniques, Immunohistochemistry, Immunologic, Large B-Cell, leukemia, LYMPH, LYMPH NODE, Lymph Nodes, Lymphadenitis, Lymphoid Tissue, LYMPHOMA, Macrophage, Macrophages, Membrane, Membrane Glycoproteins, metabolism, Monocytes, pathology, Phagocytosis, Receptor, Receptors, SIALOADHESIN, SPLEEN, Team-Mueller, tumor, Tumor Markers
@article{marmey_cd14_2006,
title = {CD14 and CD169 expression in human lymph nodes and spleen: specific expansion of CD14+C},
author = {B Marmey and C Boix and J B Barbaroux and M C Dieu-Nosjean and J Diebold and J Audouin and W H Fridman and C G Mueller and T J Molina},
year = {2006},
date = {2006-01-01},
journal = {Hum.Pathol.},
volume = {37},
number = {0046-8177 (Print)},
pages = {68--77},
abstract = {The mononuclear phagocyte system of human lymphoid tissue comprises macrophages and dendritic cells (DCs). The heterogeneity of the non-DC mononuclear phagocyte population in human lymphoid tissue has been little addressed. Here, we studied the expression of 2 monocyte-derived markers, CD14 and CD169 (sialoadhesin), in reactive human lymphoid tissue as well as in a series of 51 B-cell lymphomas by immunohistochemistry on paraffin-embedded tissue. We confirmed that lymph node sinusoidal monocyte-derived cells were the only population staining for CD169. Although most sinusoidal histiocytes also expressed CD14, monocyte-derived cells with phagocytosis such as erythrophagocytosis, anthracosis, or tingible bodies macrophage lacked CD14 and CD169. Among B-cell lymphomas, splenic marginal zone lymphoma was the only one associated with an expansion of the CD14(+)CD169(+) cells in the cords. With respect to nodal B-cell lymphomas, CD14(+) cells were rare among B-chronic lymphocytic leukemia, follicular lymphoma (FL), mantle cell lymphoma (MCL). However, strikingly, we found a strong expansion of CD14(+)CD169(-) cells in numerous diffuse large B-cell lymphomas (DLBCLs), except in cases associated with numerous mitoses, apoptotic bodies, and tingible bodies macrophages. When cultivated in granulocyte/macrophage colony stimulating factor/interleukin 4, DLBCL purified CD14(+) cells differentiate into plasmacytoid cells, expressing DC-specific intercellular adhesion molecule 3-grabbing nonintegrin, suggesting dendritic cell differentiation potential. Our observation fits well with the lymph node and host response cluster signatures described in the gene profiling signatures of DLBCL. However, the role of this CD14(+) population that may constitute a microenvironment-related marker of this subgroup of DLBCL remains to be determined},
keywords = {Adhesion, Antigen, Antigens, B-Cell, Biological, CD14, Cell Differentiation, CELL SEPARATION, Dendritic Cells, Differentiation, Diffuse, Direct, Expression, Flow Cytometry, Fluorescent Antibody Technique, Gene, GLYCOPROTEIN, Glycoproteins, granulocyte/macrophage-colony, Human, Humans, Immunoenzyme Techniques, Immunohistochemistry, Immunologic, Large B-Cell, leukemia, LYMPH, LYMPH NODE, Lymph Nodes, Lymphadenitis, Lymphoid Tissue, LYMPHOMA, Macrophage, Macrophages, Membrane, Membrane Glycoproteins, metabolism, Monocytes, pathology, Phagocytosis, Receptor, Receptors, SIALOADHESIN, SPLEEN, Team-Mueller, tumor, Tumor Markers},
pubstate = {published},
tppubtype = {article}
}
2005
Dumortier Hélène, van Mierlo Geertje J D, Egan Deirdre, van Ewijk Willem, Toes René E M, Offringa Rienk, Melief Cornelis J M
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 2, pp. 855–863, 2005, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Adenovirus E1A Proteins, Animals, Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Cell Movement, Clonal Deletion, Cytotoxic, Cytotoxicity, Dendritic Cells, Down-Regulation, Dumortier, Epitopes, Female, I2CT, Immunologic, Immunologic Memory, Inbred C57BL, Lipopolysaccharides, Lymphocyte Activation, Mice, Myeloid Cells, Receptors, Regulatory, T-Cell, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic
@article{dumortier_antigen_2005,
title = {Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like Ŧ cells that can be rescued for full effector function},
author = {Hélène Dumortier and Geertje J D van Mierlo and Deirdre Egan and Willem van Ewijk and René E M Toes and Rienk Offringa and Cornelis J M Melief},
doi = {10.4049/jimmunol.175.2.855},
issn = {0022-1767},
year = {2005},
date = {2005-01-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {175},
number = {2},
pages = {855--863},
abstract = {Immature dendritic cells (DC), in contrast to their mature counterparts, are incapable of mobilizing a CD8+ CTL response, and, instead, have been reported to induce CTL tolerance. We directly addressed the impact of immature vs mature DC on CTL responses by infusing adenovirus peptide-loaded DC (of the D1 cell line) into mice that had received adenovirus-specific naive TCR-transgenic CD8+ T cells. Whereas i.v. injection of mature DC triggered vigorous CTL expansion, immature DC elicited little proliferation involving only a minority of the TCR-transgenic CTL. Even though the latter CTL developed effector functions, including cytolytic activity and proinflammatory cytokine secretion, these cells differed significantly from CTL primed by mature DC in that they did not exhibit down-regulation of CD62L and CCR7, receptors involved in trapping of T cells in the lymphoid organs. Interestingly, adoptive transfer of CTL effector cells harvested after priming by either mature or immature DC into naive recipient mice, followed by exposure to adenovirus, yielded quantitatively and qualitatively indistinguishable CTL memory responses. Therefore, in vivo priming of naive CD8+ T cells by immature DC, although failing to induce a full-blown, systemic CTL response, resulted in the formation of central memory-like T cells that were able to expand and produce IFN-gamma upon secondary antigenic stimulation.},
keywords = {Adenovirus E1A Proteins, Animals, Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Cell Movement, Clonal Deletion, Cytotoxic, Cytotoxicity, Dendritic Cells, Down-Regulation, Dumortier, Epitopes, Female, I2CT, Immunologic, Immunologic Memory, Inbred C57BL, Lipopolysaccharides, Lymphocyte Activation, Mice, Myeloid Cells, Receptors, Regulatory, T-Cell, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic},
pubstate = {published},
tppubtype = {article}
}
Bianco Alberto, Hoebeke Johan, Godefroy Sylvie, Chaloin Olivier, Pantarotto Davide, Briand Jean-Paul, Muller Sylviane, Prato Maurizio, Partidos Charalambos D
Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties Journal Article
In: Journal of the American Chemical Society, vol. 127, no. 1, pp. 58–59, 2005, ISSN: 0002-7863.
Abstract | Links | BibTeX | Tags: Adjuvants, Animals, carbon, Cations, CpG Islands, I2CT, Immunologic, Interferon-gamma, Interleukin-6, Kinetics, Lymphocytes, Mice, Nanotubes, oligonucleotides, Surface Plasmon Resonance, Team-Bianco
@article{bianco_cationic_2005,
title = {Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties},
author = {Alberto Bianco and Johan Hoebeke and Sylvie Godefroy and Olivier Chaloin and Davide Pantarotto and Jean-Paul Briand and Sylviane Muller and Maurizio Prato and Charalambos D Partidos},
doi = {10.1021/ja044293y},
issn = {0002-7863},
year = {2005},
date = {2005-01-01},
journal = {Journal of the American Chemical Society},
volume = {127},
number = {1},
pages = {58--59},
abstract = {Functionalized cationic carbon nanotubes are able to form a stable complex with CpG ODN based on charge interaction and to increase the immunostimulatory activity of CpG motifs.},
keywords = {Adjuvants, Animals, carbon, Cations, CpG Islands, I2CT, Immunologic, Interferon-gamma, Interleukin-6, Kinetics, Lymphocytes, Mice, Nanotubes, oligonucleotides, Surface Plasmon Resonance, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
2004
van Mierlo Geertje J D, Boonman Zita F H M, Dumortier Hélène M H, den Boer Annemieke Th, Fransen Marieke F, Nouta Jan, van der Voort Ellen I H, Offringa Rienk, Toes René E M, Melief Cornelis J M
Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication Journal Article
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 173, no. 11, pp. 6753–6759, 2004, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral
@article{van_mierlo_activation_2004,
title = {Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication},
author = {Geertje J D van Mierlo and Zita F H M Boonman and Hélène M H Dumortier and Annemieke Th den Boer and Marieke F Fransen and Jan Nouta and Ellen I H van der Voort and Rienk Offringa and René E M Toes and Cornelis J M Melief},
doi = {10.4049/jimmunol.173.11.6753},
issn = {0022-1767},
year = {2004},
date = {2004-12-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {173},
number = {11},
pages = {6753--6759},
abstract = {The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.},
keywords = {Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral},
pubstate = {published},
tppubtype = {article}
}
2003
Royet Julien, Reichhart Jean-Marc
Detection of peptidoglycans by NOD proteins Journal Article
In: Trends Cell Biol., vol. 13, no. 12, pp. 610–614, 2003, ISSN: 0962-8924.
Abstract | BibTeX | Tags: Adaptor Proteins, Apoptosis, Carrier Proteins, Gram-Positive Bacteria, Humans, Immunity, Immunologic, Innate, M3i, Nod1 Signaling Adaptor Protein, Oligopeptides, peptidoglycan, Receptors, reichhart, Signal Transducing, Signal Transduction
@article{royet_detection_2003,
title = {Detection of peptidoglycans by NOD proteins},
author = {Julien Royet and Jean-Marc Reichhart},
issn = {0962-8924},
year = {2003},
date = {2003-12-01},
journal = {Trends Cell Biol.},
volume = {13},
number = {12},
pages = {610--614},
abstract = {Mechanisms of innate immune defense are based on the recognition of invariant microbial molecular patterns by specific receptors, followed by the activation of signaling pathways and the expression of effector molecules that will defeat the invading microorganism. Two recent reports add to the growing list of these pattern-recognition receptors by showing that the intracellular nucleotide-binding oligomerization domain 1 (NOD1) protein recognizes a diaminopimelate-containing muropeptide, a cell-wall component of Gram-negative bacteria.},
keywords = {Adaptor Proteins, Apoptosis, Carrier Proteins, Gram-Positive Bacteria, Humans, Immunity, Immunologic, Innate, M3i, Nod1 Signaling Adaptor Protein, Oligopeptides, peptidoglycan, Receptors, reichhart, Signal Transducing, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Kambris Zakaria, Bilak Hana, D'Alessandro Rosalba, Belvin Marcia, Imler Jean-Luc, Capovilla Maria
DmMyD88 controls dorsoventral patterning of the Drosophila embryo Journal Article
In: EMBO reports, vol. 4, no. 1, pp. 64–69, 2003, ISSN: 1469-221X.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Alleles, Animals, Antigens, Base Sequence, Cell Surface, Complementary, Developmental, Differentiation, DNA, DNA Transposable Elements, Egg Proteins, Embryo, Exons, Female, Gene Expression Regulation, Genetically Modified, Genotype, imler, Immunity, Immunologic, Innate, Insertional, M3i, Male, messenger, Morphogenesis, Mutagenesis, Myeloid Differentiation Factor 88, Nonmammalian, Oocytes, Protein Biosynthesis, Protein Structure, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Signal Transducing, Tertiary, Toll-Like Receptors, Zygote
@article{kambris_dmmyd88_2003,
title = {DmMyD88 controls dorsoventral patterning of the Drosophila embryo},
author = {Zakaria Kambris and Hana Bilak and Rosalba D'Alessandro and Marcia Belvin and Jean-Luc Imler and Maria Capovilla},
doi = {10.1038/sj.embor.embor714},
issn = {1469-221X},
year = {2003},
date = {2003-01-01},
journal = {EMBO reports},
volume = {4},
number = {1},
pages = {64--69},
abstract = {MyD88 is an adapter protein in the signal transduction pathway mediated by interleukin-1 (IL-1) and Toll-like receptors. A Drosophila homologue of MyD88 (DmMyD88) was recently shown to be required for the Toll-mediated immune response. In Drosophila, the Toll pathway was originally characterized for its role in the dorsoventral patterning of the embryo. We found that, like Toll, DmMyD88 messenger RNA is maternally supplied to the embryo. Here we report the identification of a new mutant allele of DmMyD88, which generates a protein lacking the carboxy-terminal extension, normally located downstream of the Toll/IL-1 receptor domain. Homozygous mutant female flies lay dorsalized embryos that are rescued by expression of a transgenic DmMyD88 complementary DNA. The DmMyD88 mutation blocks the ventralizing activity of a gain-of-function Toll mutation. These results show that DmMyD88 encodes an essential component of the Toll pathway in dorsoventral pattern formation.},
keywords = {Adaptor Proteins, Alleles, Animals, Antigens, Base Sequence, Cell Surface, Complementary, Developmental, Differentiation, DNA, DNA Transposable Elements, Egg Proteins, Embryo, Exons, Female, Gene Expression Regulation, Genetically Modified, Genotype, imler, Immunity, Immunologic, Innate, Insertional, M3i, Male, messenger, Morphogenesis, Mutagenesis, Myeloid Differentiation Factor 88, Nonmammalian, Oocytes, Protein Biosynthesis, Protein Structure, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Signal Transducing, Tertiary, Toll-Like Receptors, Zygote},
pubstate = {published},
tppubtype = {article}
}
2002
Ligoxygakis Petros, Bulet Philippe, Reichhart Jean-Marc
Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila Journal Article
In: EMBO Rep., vol. 3, no. 7, pp. 666–673, 2002, ISSN: 1469-221X.
Abstract | Links | BibTeX | Tags: Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Cell Adhesion Molecules, Fat Body, Gene Expression Regulation, Genes, Immunohistochemistry, Immunologic, Insect, Insect Proteins, Larva, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Membrane Proteins, Receptors, reichhart, Reporter, Spectrometry, Transgenes
@article{ligoxygakis_critical_2002,
title = {Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila},
author = {Petros Ligoxygakis and Philippe Bulet and Jean-Marc Reichhart},
doi = {10.1093/embo-reports/kvf130},
issn = {1469-221X},
year = {2002},
date = {2002-01-01},
journal = {EMBO Rep.},
volume = {3},
number = {7},
pages = {666--673},
abstract = {Essential aspects of innate immune responses to microbial infections appear to be conserved between insects and mammals. In particular, in both groups, transmembrane receptors of the Toll superfamily play a crucial role in activating immune defenses. The Drosophila Toll family member 18-Wheeler had been proposed to sense Gram-negative infection and direct selective expression of peptides active against Gram-negative bacteria. Here we re-examine the role of 18-Wheeler and show that in adults it is dispensable for immune responses. In larvae, 18wheeler is required for normal fat body development, and in mutant larvae induction of all antimicrobial peptide genes, and not only of those directed against Gram-negative bacteria, is compromised. 18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria.},
keywords = {Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Cell Adhesion Molecules, Fat Body, Gene Expression Regulation, Genes, Immunohistochemistry, Immunologic, Insect, Insect Proteins, Larva, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Membrane Proteins, Receptors, reichhart, Reporter, Spectrometry, Transgenes},
pubstate = {published},
tppubtype = {article}
}
Tauszig-Delamasure Servane, Bilak Hana, Capovilla Maria, Hoffmann Jules A, Imler Jean-Luc
Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections Journal Article
In: Nature Immunology, vol. 3, no. 1, pp. 91–97, 2002, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection
@article{tauszig-delamasure_drosophila_2002,
title = {Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections},
author = {Servane Tauszig-Delamasure and Hana Bilak and Maria Capovilla and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni747},
issn = {1529-2908},
year = {2002},
date = {2002-01-01},
journal = {Nature Immunology},
volume = {3},
number = {1},
pages = {91--97},
abstract = {We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.},
keywords = {Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection},
pubstate = {published},
tppubtype = {article}
}
2001
Imler Jean-Luc, Hoffmann Jules A
Toll receptors in innate immunity Journal Article
In: Trends in Cell Biology, vol. 11, no. 7, pp. 304–311, 2001, ISSN: 0962-8924.
Abstract | BibTeX | Tags: Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors
@article{imler_toll_2001,
title = {Toll receptors in innate immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {0962-8924},
year = {2001},
date = {2001-01-01},
journal = {Trends in Cell Biology},
volume = {11},
number = {7},
pages = {304--311},
abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals.},
keywords = {Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
2000
Imler Jean-Luc, Hoffmann Jules A
Toll and Toll-like proteins: an ancient family of receptors signaling infection Journal Article
In: Reviews in Immunogenetics, vol. 2, no. 3, pp. 294–304, 2000, ISSN: 1398-1714.
Abstract | BibTeX | Tags: Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins
@article{imler_toll_2000,
title = {Toll and Toll-like proteins: an ancient family of receptors signaling infection},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {1398-1714},
year = {2000},
date = {2000-01-01},
journal = {Reviews in Immunogenetics},
volume = {2},
number = {3},
pages = {294--304},
abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.},
keywords = {Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins},
pubstate = {published},
tppubtype = {article}
}
1996
Hoffmann Jules A, Reichhart Jean-Marc, Hetru Charles
Innate immunity in higher insects Journal Article
In: Curr. Opin. Immunol., vol. 8, no. 1, pp. 8–13, 1996, ISSN: 0952-7915.
Abstract | BibTeX | Tags: Animals, Base Sequence, Cyclic, hoffmann, Immunity, Immunologic, Immunological, Innate, insects, M3i, Models, Peptide Hydrolases, Peptides, Receptors, reichhart
@article{hoffmann_innate_1996,
title = {Innate immunity in higher insects},
author = {Jules A Hoffmann and Jean-Marc Reichhart and Charles Hetru},
issn = {0952-7915},
year = {1996},
date = {1996-02-01},
journal = {Curr. Opin. Immunol.},
volume = {8},
number = {1},
pages = {8--13},
abstract = {The hallmark of the innate immune response of higher insects is the rapid and transient synthesis of a battery of broad spectrum antimicrobial peptides by the fat body. The control of the genes encoding these peptides involves cis-regulatory promoter elements homologous to sequences functional in mammalian acute-phase genes. Study of immune-deficient mutants of Drosophila has indicated that distinct pathways control the antibacterial and antifungal responses in this species. Novel receptors potentially involved in the initiation of the immune response have been recently characterized.},
keywords = {Animals, Base Sequence, Cyclic, hoffmann, Immunity, Immunologic, Immunological, Innate, insects, M3i, Models, Peptide Hydrolases, Peptides, Receptors, reichhart},
pubstate = {published},
tppubtype = {article}
}