Publications
2015
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}
}
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, Antigen-Presenting Cells, C-Type, Cell Adhesion Molecules, Cell Surface, Cells, Confocal, Cultured, Cytokines, Dengue, Dengue virus, Enzyme-Linked Immunosorbent Assay, Epidermis, Humans, I2CT, Imagerie, Interleukin-4, Langerhans Cells, Lectins, Lymphocyte Activation, Macrophages, Microscopy, Receptors, Sensitivity and Specificity, Skin Diseases, Team-Mueller, Viral
@article{schaeffer_dermal_2015,
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 = {2015-01-01},
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, Antigen-Presenting Cells, C-Type, Cell Adhesion Molecules, Cell Surface, Cells, Confocal, Cultured, Cytokines, Dengue, Dengue virus, Enzyme-Linked Immunosorbent Assay, Epidermis, Humans, I2CT, Imagerie, Interleukin-4, Langerhans Cells, Lectins, Lymphocyte Activation, Macrophages, Microscopy, Receptors, Sensitivity and Specificity, Skin Diseases, Team-Mueller, Viral},
pubstate = {published},
tppubtype = {article}
}
2012
Flacher V, Tripp C H, Haid B, Kissenpfennig A, Malissen B, Stoitzner P, Idoyaga J, Romani N
Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses Journal Article
In: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), pp. 2146–2155, 2012.
Abstract | BibTeX | Tags: administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic
@article{flacher_skin_2012,
title = {Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses},
author = {V Flacher and C H Tripp and B Haid and A Kissenpfennig and B Malissen and P Stoitzner and J Idoyaga and N Romani},
year = {2012},
date = {2012-03-01},
journal = {Journal of Immunology},
volume = {188},
number = {1550-6606 (Electronic)},
pages = {2146--2155},
abstract = {Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerin(neg) DCs, and dermal Langerin(+) DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8alpha(+) DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin(+) DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin(+) skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin(+) skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerin(neg) dermal DCs and CD8alpha(+) DCs are sufficient to subsequent CD8(+) T cell responses},
keywords = {administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic},
pubstate = {published},
tppubtype = {article}
}
2011
Nehme Nadine T, Quintin Jessica, Cho Ju Hyun, Lee Janice, Lafarge Marie-Céline, Kocks Christine, Ferrandon Dominique
Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections Journal Article
In: PLoS ONE, vol. 6, no. 3, pp. e14743, 2011, ISSN: 1932-6203.
Abstract | Links | BibTeX | Tags: Animals, Antimicrobial Cationic Peptides, Carrier Proteins, Cell Surface, Cellular, Enterococcus faecalis, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Humoral, Immunity, Innate, M3i, Micrococcus luteus, Opsonin Proteins, Phagocytosis, Receptors, Signal Transduction, Solubility, Staphylococcus aureus
@article{nehme_relative_2011b,
title = {Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections},
author = {Nadine T Nehme and Jessica Quintin and Ju Hyun Cho and Janice Lee and Marie-Céline Lafarge and Christine Kocks and Dominique Ferrandon},
doi = {10.1371/journal.pone.0014743},
issn = {1932-6203},
year = {2011},
date = {2011-01-01},
journal = {PLoS ONE},
volume = {6},
number = {3},
pages = {e14743},
abstract = {BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.},
keywords = {Animals, Antimicrobial Cationic Peptides, Carrier Proteins, Cell Surface, Cellular, Enterococcus faecalis, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Humoral, Immunity, Innate, M3i, Micrococcus luteus, Opsonin Proteins, Phagocytosis, Receptors, Signal Transduction, Solubility, Staphylococcus aureus},
pubstate = {published},
tppubtype = {article}
}
Canard B, Vachon H, Fontaine T, Pin J J, Paul S, Genin C, Mueller C G
Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue Journal Article
In: Immunol.Lett., vol. 135, no. 1879-0542 (Electronic), pp. 165–172, 2011.
Abstract | BibTeX | Tags: Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus
@article{canard_generation_2011,
title = {Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue},
author = {B Canard and H Vachon and T Fontaine and J J Pin and S Paul and C Genin and C G Mueller},
year = {2011},
date = {2011-01-01},
journal = {Immunol.Lett.},
volume = {135},
number = {1879-0542 (Electronic)},
pages = {165--172},
abstract = {DC-SIGN is a C-type lectin of recognized importance in immunology and in the pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN have been generated, but their systemic characterization for interfering with binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far, no anti-DC-SIGN monoclonal antibody has been described that recognizes its antigen after formalin fixation and paraffin embedding. In this study, we have generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin-fixed dendritic cells and macrophages. Using this antibody we have obtained specific labelling of DC-SIGN and colocalisation with the dermal macrophage marker CD163 on human skin. The described monoclonal anti-human DC-SIGN antibodies will be of use to the scientific community to address fundamental immunology issues, in particular concerning macrophages and dendritic cells, and help elucidate infection events of pathogen targeting DC-SIGN as recognition receptor},
keywords = {Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus},
pubstate = {published},
tppubtype = {article}
}
2010
den Bossche Jeroen Van, Al-Jamal Wafa' T, Tian Bowen, Nunes Antonio, Fabbro Chiara, Bianco Alberto, Prato Maurizio, Kostarelos Kostas
Efficient receptor-independent intracellular translocation of aptamers mediated by conjugation to carbon nanotubes Journal Article
In: Chemical Communications (Cambridge, England), vol. 46, no. 39, pp. 7379–7381, 2010, ISSN: 1364-548X.
Abstract | Links | BibTeX | Tags: Aptamers, Base Sequence, Biological Transport, carbon, Cell Line, Cell Surface, DNA Primers, Electron, Electrophoresis, Humans, I2CT, Microscopy, Nanotubes, Nucleotide, Polyacrylamide Gel, Receptors, Team-Bianco, Transmission, tumor
@article{van_den_bossche_efficient_2010,
title = {Efficient receptor-independent intracellular translocation of aptamers mediated by conjugation to carbon nanotubes},
author = {Jeroen Van den Bossche and Wafa' T Al-Jamal and Bowen Tian and Antonio Nunes and Chiara Fabbro and Alberto Bianco and Maurizio Prato and Kostas Kostarelos},
doi = {10.1039/c0cc02092c},
issn = {1364-548X},
year = {2010},
date = {2010-10-01},
journal = {Chemical Communications (Cambridge, England)},
volume = {46},
number = {39},
pages = {7379--7381},
abstract = {We have covalently grafted aptamers onto carboxylated carbon nanotubes to design a novel vector system that can easily translocate into the cytosol of different cell types independent of receptor-mediated uptake. We propose the use of carbon nanotubes for the efficient intracellular delivery of biologically active aptamers for potential therapeutic applications.},
keywords = {Aptamers, Base Sequence, Biological Transport, carbon, Cell Line, Cell Surface, DNA Primers, Electron, Electrophoresis, Humans, I2CT, Microscopy, Nanotubes, Nucleotide, Polyacrylamide Gel, Receptors, Team-Bianco, Transmission, tumor},
pubstate = {published},
tppubtype = {article}
}
2008
Kwan Wing-Hong, Navarro-Sanchez Erika, Dumortier Hélène, Decossas Marion, Vachon Hortense, dos Santos Flavia Barreto, Fridman Hervé W, Rey Félix A, Harris Eva, Despres Philippe, Mueller Christopher G
Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth Journal Article
In: PLoS neglected tropical diseases, vol. 2, no. 10, pp. e311, 2008, ISSN: 1935-2735.
Abstract | Links | BibTeX | Tags: Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus
@article{kwan_dermal-type_2008b,
title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},
author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},
doi = {10.1371/journal.pntd.0000311},
issn = {1935-2735},
year = {2008},
date = {2008-10-01},
journal = {PLoS neglected tropical diseases},
volume = {2},
number = {10},
pages = {e311},
abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection.
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},
keywords = {Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus},
pubstate = {published},
tppubtype = {article}
}
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.
Flacher Vincent, Douillard Patrice, Aït-Yahia Smina, Stoitzner Patrizia, Clair-Moninot Valérie, Romani Nikolaus, Saeland Sem
Expression of langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains Journal Article
In: Immunology, vol. 123, no. 3, pp. 339–347, 2008, ISSN: 1365-2567.
Abstract | Links | BibTeX | Tags: Animals, Antigen, Antigens, C-Type, CD, Cell Surface, Dendritic Cells, DERMATOLOGY, Epidermis, Expression, Immunology, Immunophenotyping, Inbred Strains, inflammation, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Lymphoid Tissue, Mannose-Binding Lectins, Maturation, metabolism, Mice, Minor Histocompatibility Antigens, mouse, Phenotype, Protein, Receptor, Receptors, Species Specificity, SPLEEN, SUBSETS, Surface, Team-Mueller
@article{flacher_expression_2008,
title = {Expression of langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains},
author = {Vincent Flacher and Patrice Douillard and Smina Aït-Yahia and Patrizia Stoitzner and Valérie Clair-Moninot and Nikolaus Romani and Sem Saeland},
doi = {10.1111/j.1365-2567.2007.02785.x},
issn = {1365-2567},
year = {2008},
date = {2008-03-01},
journal = {Immunology},
volume = {123},
number = {3},
pages = {339--347},
abstract = {Langerin/CD207 is expressed by a subset of dendritic cells (DC), the epithelial Langerhans cells. However, langerin is also detected among lymphoid tissue DC. Here, we describe striking differences in langerin-expressing cells between inbred mouse strains. While langerin+ cells are observed in comparable numbers and with comparable phenotypes in the epidermis, two distinct DC subsets bear langerin in peripheral, skin-draining lymph nodes of BALB/c mice (CD11c(high) CD8alpha(high) and CD11c(low) CD8alpha(low)), whereas only the latter subset is present in C57BL/6 mice. The CD11c(high) subset is detected in mesenteric lymph nodes and spleen of BALB/c mice, but is virtually absent from C57BL/6 mice. Similar differences are observed in other mouse strains. CD11c(low) langerin+ cells represent skin-derived Langerhans cells, as demonstrated by their high expression of DEC-205/CD205, maturation markers, and recruitment to skin-draining lymph nodes upon imiquimod-induced inflammation. It will be of interest to determine the role of lymphoid tissue-resident compared to skin-derived langerin+ DC.},
keywords = {Animals, Antigen, Antigens, C-Type, CD, Cell Surface, Dendritic Cells, DERMATOLOGY, Epidermis, Expression, Immunology, Immunophenotyping, Inbred Strains, inflammation, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Lymphoid Tissue, Mannose-Binding Lectins, Maturation, metabolism, Mice, Minor Histocompatibility Antigens, mouse, Phenotype, Protein, Receptor, Receptors, Species Specificity, SPLEEN, SUBSETS, Surface, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Kwan Wing-Hong, Navarro-Sanchez Erika, Dumortier Hélène, Decossas Marion, Vachon Hortense, dos Santos Flavia Barreto, Fridman Hervé W, Rey Félix A, Harris Eva, Despres Philippe, Mueller Christopher G
Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth Journal Article
In: PLoS neglected tropical diseases, vol. 2, no. 10, pp. e311, 2008, ISSN: 1935-2735.
Abstract | Links | BibTeX | Tags: C-Type, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Cultured, Dengue, Dengue virus, Dumortier, Gene Expression, Humans, I2CT, Lectins, Macrophages, Protein Binding, Receptors, Skin, Team-Dumortier, Team-Mueller, Viral Envelope Proteins
@article{kwan_dermal-type_2008,
title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},
author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},
doi = {10.1371/journal.pntd.0000311},
issn = {1935-2735},
year = {2008},
date = {2008-01-01},
journal = {PLoS neglected tropical diseases},
volume = {2},
number = {10},
pages = {e311},
abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection.
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},
keywords = {C-Type, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Cultured, Dengue, Dengue virus, Dumortier, Gene Expression, Humans, I2CT, Lectins, Macrophages, Protein Binding, Receptors, Skin, Team-Dumortier, Team-Mueller, Viral Envelope Proteins},
pubstate = {published},
tppubtype = {article}
}
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.
2005
Kocks Christine, Cho Ju Hyun, Nehme Nadine, Ulvila Johanna, Pearson Alan M, Meister Marie, Strom Charles, Conto Stephanie L, Hetru Charles, Stuart Lynda M, Stehle Thilo, Hoffmann Jules A, Reichhart Jean-Marc, Ferrandon Dominique, Rämet Mika, Ezekowitz Alan R B
Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila Journal Article
In: Cell, vol. 123, no. 2, pp. 335–346, 2005, ISSN: 0092-8674.
Abstract | Links | BibTeX | Tags: Amino Acid, Amino Acid Motifs, Animals, Bacterial Infections, Cell Surface, Embryo, Escherichia coli, ferrandon, Flow Cytometry, Frameshift Mutation, Genes, Histidine, hoffmann, In Situ Hybridization, Insect, Insect Proteins, M3i, Macrophages, Membrane Proteins, messenger, Nonmammalian, Open Reading Frames, Phagocytosis, Receptors, reichhart, RNA, RNA Interference, Sequence Homology, Serratia marcescens
@article{kocks_eater_2005,
title = {Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila},
author = {Christine Kocks and Ju Hyun Cho and Nadine Nehme and Johanna Ulvila and Alan M Pearson and Marie Meister and Charles Strom and Stephanie L Conto and Charles Hetru and Lynda M Stuart and Thilo Stehle and Jules A Hoffmann and Jean-Marc Reichhart and Dominique Ferrandon and Mika Rämet and Alan R B Ezekowitz},
doi = {10.1016/j.cell.2005.08.034},
issn = {0092-8674},
year = {2005},
date = {2005-10-01},
journal = {Cell},
volume = {123},
number = {2},
pages = {335--346},
abstract = {Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.},
keywords = {Amino Acid, Amino Acid Motifs, Animals, Bacterial Infections, Cell Surface, Embryo, Escherichia coli, ferrandon, Flow Cytometry, Frameshift Mutation, Genes, Histidine, hoffmann, In Situ Hybridization, Insect, Insect Proteins, M3i, Macrophages, Membrane Proteins, messenger, Nonmammalian, Open Reading Frames, Phagocytosis, Receptors, reichhart, RNA, RNA Interference, Sequence Homology, Serratia marcescens},
pubstate = {published},
tppubtype = {article}
}
Martinelli Cosimo, Reichhart Jean-Marc
Evolution and integration of innate immune systems from fruit flies to man: lessons and questions Journal Article
In: J. Endotoxin Res., vol. 11, no. 4, pp. 243–248, 2005, ISSN: 0968-0519.
Abstract | Links | BibTeX | Tags: Animals, Biological Evolution, Cell Surface, Forecasting, Humans, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors
@article{martinelli_evolution_2005,
title = {Evolution and integration of innate immune systems from fruit flies to man: lessons and questions},
author = {Cosimo Martinelli and Jean-Marc Reichhart},
doi = {10.1179/096805105X37411},
issn = {0968-0519},
year = {2005},
date = {2005-01-01},
journal = {J. Endotoxin Res.},
volume = {11},
number = {4},
pages = {243--248},
abstract = {Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla.},
keywords = {Animals, Biological Evolution, Cell Surface, Forecasting, Humans, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Weber Alexander N R, Moncrieffe Martin C, Gangloff Monique, Imler Jean-Luc, Gay Nicholas J
Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway Journal Article
In: The Journal of Biological Chemistry, vol. 280, no. 24, pp. 22793–22799, 2005, ISSN: 0021-9258.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation
@article{weber_ligand-receptor_2005,
title = {Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway},
author = {Alexander N R Weber and Martin C Moncrieffe and Monique Gangloff and Jean-Luc Imler and Nicholas J Gay},
doi = {10.1074/jbc.M502074200},
issn = {0021-9258},
year = {2005},
date = {2005-01-01},
journal = {The Journal of Biological Chemistry},
volume = {280},
number = {24},
pages = {22793--22799},
abstract = {In Drosophila, the signaling pathway mediated by the Toll receptor is critical for the establishment of embryonic dorso-ventral pattern and for innate immune responses to bacterial and fungal pathogens. Toll is activated by high affinity binding of the cytokine Spätzle, a dimeric ligand of the cystine knot family. In vertebrates, a related family of Toll-like receptors play a critical role in innate immune responses. Despite the importance of this family of receptors, little is known about the biochemical events that lead to receptor activation and signaling. Here, we show that Spätzle binds to the N-terminal region of Toll and, using biophysical methods, that the binding is complex. The two binding events that cause formation of the cross-linked complex are non-equivalent: the first Toll ectodomain binds Spätzle with an affinity 3-fold higher than the second molecule suggesting that pathway activation involves negative cooperativity. We further show that the Toll ectodomains are able to form low affinity dimers in solution and that juxtamembrane sequences of Toll are critical for the activation or derepression of the pathway. These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions.},
keywords = {Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation},
pubstate = {published},
tppubtype = {article}
}
2004
Bischoff Vincent, Vignal Cécile, Boneca Ivo G, Michel Tatiana, Hoffmann Jules A, Royet Julien
Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria Journal Article
In: Nat. Immunol., vol. 5, no. 11, pp. 1175–1180, 2004, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Carrier Proteins, Cell Surface, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, hoffmann, M3i, Mutation, Mycoses, Receptors, Staphylococcus aureus, Toll-Like Receptors
@article{bischoff_function_2004,
title = {Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria},
author = {Vincent Bischoff and Cécile Vignal and Ivo G Boneca and Tatiana Michel and Jules A Hoffmann and Julien Royet},
doi = {10.1038/ni1123},
issn = {1529-2908},
year = {2004},
date = {2004-11-01},
journal = {Nat. Immunol.},
volume = {5},
number = {11},
pages = {1175--1180},
abstract = {The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-positive bacterial species activate an immune response in a PGRP-SA- and GNBP1-independent manner, indicating that alternative receptors exist. Consistent with this, we noted that PGRP-SD mutants were susceptible to some Gram-positive bacteria and that a loss-of-function mutation in PGRP-SD severely exacerbated the PGRP-SA and GNBP1 mutant phenotypes. These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex.},
keywords = {Animals, Carrier Proteins, Cell Surface, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, hoffmann, M3i, Mutation, Mycoses, Receptors, Staphylococcus aureus, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Leclerc Vincent, Reichhart Jean-Marc
The immune response of Drosophila melanogaster Journal Article
In: Immunol. Rev., vol. 198, pp. 59–71, 2004, ISSN: 0105-2896.
Abstract | BibTeX | Tags: Animals, Cell Surface, Immunity, Immunological, Innate, M3i, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors
@article{leclerc_immune_2004,
title = {The immune response of Drosophila melanogaster},
author = {Vincent Leclerc and Jean-Marc Reichhart},
issn = {0105-2896},
year = {2004},
date = {2004-04-01},
journal = {Immunol. Rev.},
volume = {198},
pages = {59--71},
abstract = {The response of the fruit fly Drosophila melanogaster to various microorganism infections relies on a multilayered defense. The epithelia constitute a first and efficient barrier. Innate immunity is activated when microorganisms succeed in entering the body cavity of the fly. Invading microorganisms are killed by the combined action of cellular and humoral processes. They are phagocytosed by specialized blood cells, surrounded by toxic melanin, or lysed by antibacterial peptides secreted into the hemolymph by fat body cells. During the last few years, research has focused on the mechanisms of microbial recognition by various pattern recognition receptors and of the subsequent induction of antimicrobial peptide expression. The cellular arm of the Drosophila innate immune system, which was somehow neglected, now constitutes the new frontier.},
keywords = {Animals, Cell Surface, Immunity, Immunological, Innate, M3i, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Zheng Liangbiao
Biology of Toll receptors: lessons from insects and mammals Journal Article
In: Journal of Leukocyte Biology, vol. 75, no. 1, pp. 18–26, 2004, ISSN: 0741-5400.
Abstract | Links | BibTeX | Tags: Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors
@article{imler_biology_2004,
title = {Biology of Toll receptors: lessons from insects and mammals},
author = {Jean-Luc Imler and Liangbiao Zheng},
doi = {10.1189/jlb.0403160},
issn = {0741-5400},
year = {2004},
date = {2004-01-01},
journal = {Journal of Leukocyte Biology},
volume = {75},
number = {1},
pages = {18--26},
abstract = {Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.},
keywords = {Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Ferrandon Dominique, Royet Julien, Reichhart Jean-Marc, Hetru Charles, Hoffmann Jules A
Toll-dependent and Toll-independent immune responses in Drosophila Journal Article
In: Journal of Endotoxin Research, vol. 10, no. 4, pp. 241–246, 2004, ISSN: 0968-0519.
Abstract | Links | BibTeX | Tags: Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation
@article{imler_toll-dependent_2004,
title = {Toll-dependent and Toll-independent immune responses in Drosophila},
author = {Jean-Luc Imler and Dominique Ferrandon and Julien Royet and Jean-Marc Reichhart and Charles Hetru and Jules A Hoffmann},
doi = {10.1179/096805104225005887},
issn = {0968-0519},
year = {2004},
date = {2004-01-01},
journal = {Journal of Endotoxin Research},
volume = {10},
number = {4},
pages = {241--246},
abstract = {The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs.},
keywords = {Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
2003
Ligoxygakis Petros, Roth Siegfried, Reichhart Jean-Marc
A serpin regulates dorsal-ventral axis formation in the Drosophila embryo Journal Article
In: Curr. Biol., vol. 13, no. 23, pp. 2097–2102, 2003, ISSN: 0960-9822.
Abstract | BibTeX | Tags: Animals, Body Patterning, Cell Surface, Crosses, Female, Genetic, Immunohistochemistry, M3i, Microinjections, Receptors, reichhart, Serine Proteinase Inhibitors, Serpins, Signal Transduction, Toll-Like Receptors
@article{ligoxygakis_serpin_2003,
title = {A serpin regulates dorsal-ventral axis formation in the Drosophila embryo},
author = {Petros Ligoxygakis and Siegfried Roth and Jean-Marc Reichhart},
issn = {0960-9822},
year = {2003},
date = {2003-12-01},
journal = {Curr. Biol.},
volume = {13},
number = {23},
pages = {2097--2102},
abstract = {Extracellular serine protease cascades have evolved in vertebrates and invertebrates to mediate rapid, local reactions to physiological or pathological cues. The serine protease cascade that triggers the Toll signaling pathway in Drosophila embryogenesis shares several organizational characteristics with those involved in mammalian complement and blood clotting. One of the hallmarks of such cascades is their regulation by serine protease inhibitors (serpins). Serpins act as suicide substrates and are cleaved by their target protease, forming an essentially irreversible 1:1 complex. The biological importance of serpins is highlighted by serpin dysfunction diseases, such as thrombosis caused by a deficiency in antithrombin. Here, we describe how a serpin controls the serine protease cascade, leading to Toll pathway activation. Female flies deficient in Serpin-27A produce embryos that lack dorsal-ventral polarity and show uniform high levels of Toll signaling. Since this serpin has been recently shown to restrain an immune reaction in the blood of Drosophila, it demonstrates that proteolysis can be regulated by the same serpin in different biological contexts.},
keywords = {Animals, Body Patterning, Cell Surface, Crosses, Female, Genetic, Immunohistochemistry, M3i, Microinjections, Receptors, reichhart, Serine Proteinase Inhibitors, Serpins, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Reichhart Jean-Marc
TLR5 takes aim at bacterial propeller Journal Article
In: Nat. Immunol., vol. 4, no. 12, pp. 1159–1160, 2003, ISSN: 1529-2908.
Links | BibTeX | Tags: Animals, Bacterial Physiological Phenomena, Cell Surface, Flagella, Flagellin, Humans, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors
@article{reichhart_tlr5_2003,
title = {TLR5 takes aim at bacterial propeller},
author = {Jean-Marc Reichhart},
doi = {10.1038/ni1203-1159},
issn = {1529-2908},
year = {2003},
date = {2003-12-01},
journal = {Nat. Immunol.},
volume = {4},
number = {12},
pages = {1159--1160},
keywords = {Animals, Bacterial Physiological Phenomena, Cell Surface, Flagella, Flagellin, Humans, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Gobert Vanessa, Gottar Marie, Matskevich Alexey A, Rutschmann Sophie, Royet Julien, Belvin Marcia, Hoffmann Jules A, Ferrandon Dominique
Dual activation of the Drosophila toll pathway by two pattern recognition receptors Journal Article
In: Science, vol. 302, no. 5653, pp. 2126–2130, 2003, ISSN: 1095-9203.
Abstract | Links | BibTeX | Tags: Animals, Carrier Proteins, Cell Surface, DNA Transposable Elements, ferrandon, Gene Expression, Genes, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Mutation, Phenotype, Receptors, Serine Endopeptidases, Toll-Like Receptors
@article{gobert_dual_2003,
title = {Dual activation of the Drosophila toll pathway by two pattern recognition receptors},
author = {Vanessa Gobert and Marie Gottar and Alexey A Matskevich and Sophie Rutschmann and Julien Royet and Marcia Belvin and Jules A Hoffmann and Dominique Ferrandon},
doi = {10.1126/science.1085432},
issn = {1095-9203},
year = {2003},
date = {2003-12-01},
journal = {Science},
volume = {302},
number = {5653},
pages = {2126--2130},
abstract = {The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects.},
keywords = {Animals, Carrier Proteins, Cell Surface, DNA Transposable Elements, ferrandon, Gene Expression, Genes, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Mutation, Phenotype, Receptors, Serine Endopeptidases, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Goto Akira, Blandin Stéphanie A, Royet Julien, Reichhart Jean-Marc, Levashina Elena A
Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies Journal Article
In: Nucleic Acids Res., vol. 31, no. 22, pp. 6619–6623, 2003, ISSN: 1362-4962.
Abstract | BibTeX | Tags: Animals, blandin, Cell Surface, Double-Stranded, Epistasis, Female, Genetic, Green Fluorescent Proteins, Homeodomain Proteins, Luminescent Proteins, M3i, Phenotype, Receptors, reichhart, RNA, RNA Interference, Serpins, Signal Transduction, Time Factors, Toll-Like Receptors, Transcription Factors
@article{goto_silencing_2003,
title = {Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies},
author = {Akira Goto and Stéphanie A Blandin and Julien Royet and Jean-Marc Reichhart and Elena A Levashina},
issn = {1362-4962},
year = {2003},
date = {2003-11-01},
journal = {Nucleic Acids Res.},
volume = {31},
number = {22},
pages = {6619--6623},
abstract = {Double-stranded RNA (dsRNA) gene interference is an efficient method to silence gene expression in a sequence-specific manner. Here we show that the direct injection of dsRNA can be used in adult Drosophila flies to disrupt function of endogenous genes in vivo. As a proof of principle, we have used this method to silence components of a major signaling cascade, the Toll pathway, which controls fruit fly resistance to fungal and Gram-positive bacterial infections. We demonstrate that the knockout is efficient only if dsRNA is injected in 4- or more day-old flies and that it lasts for at least 1 week. Furthermore, we report dsRNA-based epistatic gene analysis via injection of a mixture of two dsRNAs and propose that injection of dsRNA represents a powerful method for rapid functional analysis of genes in Drosophila melanogaster adults, particularly of those whose mutations are lethal during development.},
keywords = {Animals, blandin, Cell Surface, Double-Stranded, Epistasis, Female, Genetic, Green Fluorescent Proteins, Homeodomain Proteins, Luminescent Proteins, M3i, Phenotype, Receptors, reichhart, RNA, RNA Interference, Serpins, Signal Transduction, Time Factors, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Hoffmann Jules A
The immune response of Drosophila Journal Article
In: Nature, vol. 426, no. 6962, pp. 33–38, 2003, ISSN: 1476-4687.
Abstract | Links | BibTeX | Tags: Animals, Cell Surface, hoffmann, Immunity, Innate, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors
@article{hoffmann_immune_2003,
title = {The immune response of Drosophila},
author = {Jules A Hoffmann},
doi = {10.1038/nature02021},
issn = {1476-4687},
year = {2003},
date = {2003-11-01},
journal = {Nature},
volume = {426},
number = {6962},
pages = {33--38},
abstract = {Drosophila mounts a potent host defence when challenged by various microorganisms. Analysis of this defence by molecular genetics has now provided a global picture of the mechanisms by which this insect senses infection, discriminates between various classes of microorganisms and induces the production of effector molecules, among which antimicrobial peptides are prominent. An unexpected result of these studies was the discovery that most of the genes involved in the Drosophila host defence are homologous or very similar to genes implicated in mammalian innate immune defences. Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity.},
keywords = {Animals, Cell Surface, hoffmann, Immunity, Innate, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Weber Alexander N R, Tauszig-Delamasure Servane, Hoffmann Jules A, Lelièvre Eric, Gascan Hugues, Ray Keith P, Morse Mary A, Imler Jean-Luc, Gay Nicholas J
Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling Journal Article
In: Nature Immunology, vol. 4, no. 8, pp. 794–800, 2003, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Cell Surface, hoffmann, imler, Insect Proteins, M3i, Protein Binding, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors
@article{weber_binding_2003,
title = {Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling},
author = {Alexander N R Weber and Servane Tauszig-Delamasure and Jules A Hoffmann and Eric Lelièvre and Hugues Gascan and Keith P Ray and Mary A Morse and Jean-Luc Imler and Nicholas J Gay},
doi = {10.1038/ni955},
issn = {1529-2908},
year = {2003},
date = {2003-08-01},
journal = {Nature Immunology},
volume = {4},
number = {8},
pages = {794--800},
abstract = {The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Spätzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Spätzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Spätzle dimer to two receptors. The Spätzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling.},
keywords = {Animals, Cell Surface, hoffmann, imler, Insect Proteins, M3i, Protein Binding, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Bilak Hana, Tauszig-Delamasure S, Imler Jean-Luc
Toll and Toll-like receptors in Drosophila Journal Article
In: Biochemical Society Transactions, vol. 31, no. Pt 3, pp. 648–651, 2003, ISSN: 0300-5127.
Abstract | Links | BibTeX | Tags: Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors
@article{bilak_toll_2003,
title = {Toll and Toll-like receptors in Drosophila},
author = {Hana Bilak and S Tauszig-Delamasure and Jean-Luc Imler},
doi = {10.1042/},
issn = {0300-5127},
year = {2003},
date = {2003-06-01},
journal = {Biochemical Society Transactions},
volume = {31},
number = {Pt 3},
pages = {648--651},
abstract = {The Drosophila Toll receptor controls the immune response to Gram-positive bacteria and fungi by activating a signalling pathway partially conserved throughout evolution. The Drosophila genome encodes eight additional Toll-related receptors, most of which appear to carry out developmental rather than immune functions. One exception may be Toll-9, which shares structural and functional similarities with mammalian TLRs.},
keywords = {Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Luna C, Hoa N T, Zhang J, Kanzok S M, Brown S E, Imler Jean-Luc, Knudson D L, Zheng L
Characterization of three Toll-like genes from mosquito Aedes aegypti Journal Article
In: Insect Molecular Biology, vol. 12, no. 1, pp. 67–74, 2003, ISSN: 0962-1075.
Abstract | BibTeX | Tags: Aedes, Animals, Base Sequence, Cell Surface, Chimera, Cloning, Developmental, Female, Gene Expression Regulation, Genetic, imler, Insect Proteins, M3i, Male, messenger, Models, Molecular, Mutagenesis, Promoter Regions, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Sequence Alignment, Signal Transduction, Site-Directed, Transfection
@article{luna_characterization_2003,
title = {Characterization of three Toll-like genes from mosquito Aedes aegypti},
author = {C Luna and N T Hoa and J Zhang and S M Kanzok and S E Brown and Jean-Luc Imler and D L Knudson and L Zheng},
issn = {0962-1075},
year = {2003},
date = {2003-02-01},
journal = {Insect Molecular Biology},
volume = {12},
number = {1},
pages = {67--74},
abstract = {Three Toll-related genes (AeToll1A, AeToll1B and AeToll5) were cloned and characterized from the yellow fever vector mosquito, Aedes aegypti. All three genes exhibited high levels of amino acid sequence similarity with Drosophila melanogaster (Dm)Toll1 and DmTehao (Toll5). AeToll1A and AeToll1B are 1124 and 1076 amino acid residues long, respectively. Both contain a carboxyl extension downstream of the Toll/interleukin-1 receptor (TIR) domain. AeToll5 is 1007 residues long and, like DmTehao, lacks the carboxyl terminal extension. Expression of these three genes was examined throughout development and after immune challenge. Both AeToll1A and AeToll5, like their Drosophila counterparts, activate transcription of drosomycin promoter in both Aedes and Drosophila cell lines. Deletion of the carboxyl extension of AeToll1A did not result in a further elevated level of the antifungal response. The intracellular signalling process appears to be species specific based on two observations. (1) DmToll is completely inactive in an Aedes cell line, suggesting a higher specificity requirement for DmToll in the intracellular signalling process. (2) Only one of three amino acid residues essential for DmToll function is required for AeToll1A function.},
keywords = {Aedes, Animals, Base Sequence, Cell Surface, Chimera, Cloning, Developmental, Female, Gene Expression Regulation, Genetic, imler, Insect Proteins, M3i, Male, messenger, Models, Molecular, Mutagenesis, Promoter Regions, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Sequence Alignment, Signal Transduction, Site-Directed, Transfection},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Hoffmann Jules A
Toll signaling: the TIReless quest for specificity Journal Article
In: Nature Immunology, vol. 4, no. 2, pp. 105–106, 2003, ISSN: 1529-2908.
Links | BibTeX | Tags: Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors
@article{imler_toll_2003,
title = {Toll signaling: the TIReless quest for specificity},
author = {Jean-Luc Imler and Jules A Hoffmann},
doi = {10.1038/ni0203-105},
issn = {1529-2908},
year = {2003},
date = {2003-02-01},
journal = {Nature Immunology},
volume = {4},
number = {2},
pages = {105--106},
keywords = {Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors},
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, Pelte Nadège, Ji Chuanyi, Leclerc Vincent, Duvic Bernard, Belvin Marcia, Jiang Haobo, Hoffmann Jules A, Reichhart Jean-Marc
A serpin mutant links Toll activation to melanization in the host defence of Drosophila Journal Article
In: EMBO J., vol. 21, no. 23, pp. 6330–6337, 2002, ISSN: 0261-4189.
Abstract | BibTeX | Tags: Animals, Cell Surface, Hemolymph, hoffmann, infection, M3i, Melanins, Receptors, reichhart, Serpins, Toll-Like Receptors
@article{ligoxygakis_serpin_2002,
title = {A serpin mutant links Toll activation to melanization in the host defence of Drosophila},
author = {Petros Ligoxygakis and Nadège Pelte and Chuanyi Ji and Vincent Leclerc and Bernard Duvic and Marcia Belvin and Haobo Jiang and Jules A Hoffmann and Jean-Marc Reichhart},
issn = {0261-4189},
year = {2002},
date = {2002-12-01},
journal = {EMBO J.},
volume = {21},
number = {23},
pages = {6330--6337},
abstract = {A prominent response during the Drosophila host defence is the induction of proteolytic cascades, some of which lead to localized melanization of pathogen surfaces, while others activate one of the major players in the systemic antimicrobial response, the Toll pathway. Despite the fact that gain-of-function mutations in the Toll receptor gene result in melanization, a clear link between Toll activation and the melanization reaction has not been firmly established. Here, we present evidence for the coordination of hemolymph-borne melanization with activation of the Toll pathway in the Drosophila host defence. The melanization reaction requires Toll pathway activation and depends on the removal of the Drosophila serine protease inhibitor Serpin27A. Flies deficient for this serpin exhibit spontaneous melanization in larvae and adults. Microbial challenge induces its removal from the hemolymph through Toll-dependent transcription of an acute phase immune reaction component.},
keywords = {Animals, Cell Surface, Hemolymph, hoffmann, infection, M3i, Melanins, Receptors, reichhart, Serpins, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Kambris Zakaria, Hoffmann Jules A, Imler Jean-Luc, Capovilla Maria
Tissue and stage-specific expression of the Tolls in Drosophila embryos Journal Article
In: Gene expression patterns: GEP, vol. 2, no. 3-4, pp. 311–317, 2002, ISSN: 1567-133X.
Abstract | BibTeX | Tags: Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors
@article{kambris_tissue_2002,
title = {Tissue and stage-specific expression of the Tolls in Drosophila embryos},
author = {Zakaria Kambris and Jules A Hoffmann and Jean-Luc Imler and Maria Capovilla},
issn = {1567-133X},
year = {2002},
date = {2002-12-01},
journal = {Gene expression patterns: GEP},
volume = {2},
number = {3-4},
pages = {311--317},
abstract = {The Drosophila transmembrane receptor Toll plays a key role in specifying the dorsoventral axis of the embryo. At later stages of development, it controls the immune response of the fly to fungal and Gram-positive bacterial infections. The Drosophila genome has a total of nine Toll-like genes, including the previously characterized Toll (Toll-1) and 18-wheeler (Toll-2). Here we describe the embryonic expression patterns of the seven Toll-like genes Toll-3 through Toll-9. We find that these genes have distinct expression domains and that their expression is dynamically changing throughout embryonic development. This complex and tissue-specific regulation of Toll-like gene expression strongly suggests a role in embryonic development for most Drosophila Tolls. The evolving picture on the Toll family members in Drosophila contrasts with that of mammalian Toll-like receptors, which are predominantly expressed in immune responsive cells where their activation occurs via microbial structural determinants.},
keywords = {Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Ligoxygakis Petros, Pelte Nadège, Hoffmann Jules A, Reichhart Jean-Marc
Activation of Drosophila Toll during fungal infection by a blood serine protease Journal Article
In: Science, vol. 297, no. 5578, pp. 114–116, 2002, ISSN: 1095-9203.
Abstract | Links | BibTeX | Tags: Animals, Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, reichhart, Serine Endopeptidases, Tertiary, Toll-Like Receptors
@article{ligoxygakis_activation_2002,
title = {Activation of Drosophila Toll during fungal infection by a blood serine protease},
author = {Petros Ligoxygakis and Nadège Pelte and Jules A Hoffmann and Jean-Marc Reichhart},
doi = {10.1126/science.1072391},
issn = {1095-9203},
year = {2002},
date = {2002-07-01},
journal = {Science},
volume = {297},
number = {5578},
pages = {114--116},
abstract = {Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.},
keywords = {Animals, Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, reichhart, Serine Endopeptidases, Tertiary, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Hoffmann Jules A, Reichhart Jean-Marc
Drosophila innate immunity: an evolutionary perspective Journal Article
In: Nat. Immunol., vol. 3, no. 2, pp. 121–126, 2002, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors
@article{hoffmann_drosophila_2002,
title = {Drosophila innate immunity: an evolutionary perspective},
author = {Jules A Hoffmann and Jean-Marc Reichhart},
doi = {10.1038/ni0202-121},
issn = {1529-2908},
year = {2002},
date = {2002-02-01},
journal = {Nat. Immunol.},
volume = {3},
number = {2},
pages = {121--126},
abstract = {In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.},
keywords = {Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},
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}
}
Imler Jean-Luc, Hoffmann Jules A
Toll receptors in Drosophila: a family of molecules regulating development and immunity Journal Article
In: Current Topics in Microbiology and Immunology, vol. 270, pp. 63–79, 2002, ISSN: 0070-217X.
Abstract | BibTeX | Tags: Animals, Cell Surface, Genetic, Gram-Negative Bacteria, hoffmann, imler, M3i, Receptors, Signal Transduction, Toll-Like Receptors, Transcription
@article{imler_toll_2002,
title = {Toll receptors in Drosophila: a family of molecules regulating development and immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {0070-217X},
year = {2002},
date = {2002-01-01},
journal = {Current Topics in Microbiology and Immunology},
volume = {270},
pages = {63--79},
abstract = {In recent years, Toll-like receptors (TLRs) have emerged as key receptors which detect microbes and initiate an inflammatory response. The Toll receptor was originally identified and characterized 14 years ago for its role in the embryonic development of the fruit-fly Drosophila melanogaster. Subsequently, it was also shown to be an essential component of the signaling pathway mediating the anti-fungal host defense in this model organism. New factors involved in the activation of the Toll receptor or in intracytoplasmic signaling during the immune response in Drosophila have recently been identified. The existence of significant functional differences between mammalian TLRs and Drosophila Toll receptors is also becoming apparent.},
keywords = {Animals, Cell Surface, Genetic, Gram-Negative Bacteria, hoffmann, imler, M3i, Receptors, Signal Transduction, Toll-Like Receptors, Transcription},
pubstate = {published},
tppubtype = {article}
}
2001
Michel T, Reichhart Jean-Marc, Hoffmann Jules A, Royet Julien
Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein Journal Article
In: Nature, vol. 414, no. 6865, pp. 756–759, 2001, ISSN: 0028-0836.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors
@article{michel_drosophila_2001,
title = {Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein},
author = {T Michel and Jean-Marc Reichhart and Jules A Hoffmann and Julien Royet},
doi = {10.1038/414756a},
issn = {0028-0836},
year = {2001},
date = {2001-12-01},
journal = {Nature},
volume = {414},
number = {6865},
pages = {756--759},
abstract = {Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.},
keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Mueller C G, Cremer I, Paulet P E, Niida S, Maeda N, Lebeque S, Fridman W H, Sautès-Fridman C
Mannose receptor ligand-positive cells express the metalloprotease decysin in the B cell follicle Journal Article
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 167, no. 9, pp. 5052–5060, 2001, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: ADAM Proteins, Amino Acid Sequence, Animals, B-Lymphocytes, C-Type, Cell Surface, Cloning, Dendritic Cells, Follicular, Germinal Center, Humans, Inbred BALB C, Lectins, ligands, Macrophage Colony-Stimulating Factor, Macrophages, Mannose-Binding Lectins, Metalloendopeptidases, Mice, Molecular, Molecular Sequence Data, Receptors, SPLEEN, Team-Mueller
@article{mueller_mannose_2001,
title = {Mannose receptor ligand-positive cells express the metalloprotease decysin in the B cell follicle},
author = {C G Mueller and I Cremer and P E Paulet and S Niida and N Maeda and S Lebeque and W H Fridman and C Sautès-Fridman},
doi = {10.4049/jimmunol.167.9.5052},
issn = {0022-1767},
year = {2001},
date = {2001-11-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {167},
number = {9},
pages = {5052--5060},
abstract = {Decysin, a gene encoding a disintegrin metalloprotease, is transcribed in human dendritic cells (DC) and germinal centers (GC). We have cloned its murine homologue and show that it is processed by the endoprotease furin before secretion of the catalytic domain. We have defined the cell types that express decysin in mouse spleen in the course of an immune response to T cell-dependent Ags. Like in humans, decysin is transcribed by activated CD11c(+) DC that enter the T cell zone from the marginal zone (MZ). In the GC, decysin is expressed by follicular DC and tingible body macrophages. In addition, a MZ cell population expresses decysin and appears to migrate into the B cell follicle. The majority of these follicle-homing cells express the mannose receptor ligand, a marker for the macrophage-like MZ metallophils. The follicle-homing cells are M-CSF dependent, as they are absent in op/op mice that lack functional M-CSF. This suggests that mannose receptor ligand(+) MZ metallophils differentiate into cells that migrate from the MZ into the B cell follicle. Decysin represents the first marker for this previously unrecognized cell population of the mouse spleen, which may represent a precursor for GCDC and may be specialized in the transport of unprocessed Ag from the MZ into developing GC.},
keywords = {ADAM Proteins, Amino Acid Sequence, Animals, B-Lymphocytes, C-Type, Cell Surface, Cloning, Dendritic Cells, Follicular, Germinal Center, Humans, Inbred BALB C, Lectins, ligands, Macrophage Colony-Stimulating Factor, Macrophages, Mannose-Binding Lectins, Metalloendopeptidases, Mice, Molecular, Molecular Sequence Data, Receptors, SPLEEN, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
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
Lagueux Marie, Perrodou E, Levashina Elena A, Capovilla Maria, Hoffmann Jules A
Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila Journal Article
In: Proc. Natl. Acad. Sci. U.S.A., vol. 97, no. 21, pp. 11427–11432, 2000, ISSN: 0027-8424.
Abstract | Links | BibTeX | Tags: alpha-Macroglobulins, Amino Acid, Animals, Cell Surface, Complement C3, Esters, Genetic, hoffmann, Insect Proteins, Janus Kinases, M3i, Membrane Glycoproteins, Mutation, Protein-Tyrosine Kinases, Proteins, Receptors, Sequence Homology, Sulfhydryl Compounds, Toll-Like Receptors, Transcription, Transcription Factors
@article{lagueux_constitutive_2000,
title = {Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila},
author = {Marie Lagueux and E Perrodou and Elena A Levashina and Maria Capovilla and Jules A Hoffmann},
doi = {10.1073/pnas.97.21.11427},
issn = {0027-8424},
year = {2000},
date = {2000-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {97},
number = {21},
pages = {11427--11432},
abstract = {We show that Drosophila expresses four genes encoding proteins with significant similarities with the thiolester-containing proteins of the complement C3/alpha(2)-macroglobulin superfamily. The genes are transcribed at a low level during all stages of development, and their expression is markedly up-regulated after an immune challenge. For one of these genes, which is predominantly expressed in the larval fat body, we observe a constitutive expression in gain-of-function mutants of the Janus kinase (JAK) hop and a reduced inducibility in loss-of-function hop mutants. We also observe a constitutive expression in gain-of-function Toll mutants. We discuss the possible roles of these novel complement-like proteins in the Drosophila host defense.},
keywords = {alpha-Macroglobulins, Amino Acid, Animals, Cell Surface, Complement C3, Esters, Genetic, hoffmann, Insect Proteins, Janus Kinases, M3i, Membrane Glycoproteins, Mutation, Protein-Tyrosine Kinases, Proteins, Receptors, Sequence Homology, Sulfhydryl Compounds, Toll-Like Receptors, Transcription, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Rutschmann Sophie, Jung Alain C, Zhou R, Silverman N, Hoffmann Jules A, Ferrandon Dominique
Role of Drosophila IKK gamma in a toll-independent antibacterial immune response Journal Article
In: Nat. Immunol., vol. 1, no. 4, pp. 342–347, 2000, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Antigens, Bacterial, Cell Surface, ferrandon, Gene Expression Regulation, hoffmann, I-kappa B Kinase, Immunity, Innate, Insect Proteins, M3i, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factors
@article{rutschmann_role_2000,
title = {Role of Drosophila IKK gamma in a toll-independent antibacterial immune response},
author = {Sophie Rutschmann and Alain C Jung and R Zhou and N Silverman and Jules A Hoffmann and Dominique Ferrandon},
doi = {10.1038/79801},
issn = {1529-2908},
year = {2000},
date = {2000-10-01},
journal = {Nat. Immunol.},
volume = {1},
number = {4},
pages = {342--347},
abstract = {We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.},
keywords = {Animals, Antigens, Bacterial, Cell Surface, ferrandon, Gene Expression Regulation, hoffmann, I-kappa B Kinase, Immunity, Innate, Insect Proteins, M3i, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Tauszig Servane, Jouanguy Emmanuelle, Hoffmann Jules A, Imler Jean-Luc
Toll-related receptors and the control of antimicrobial peptide expression in Drosophila Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 19, pp. 10520–10525, 2000, ISSN: 0027-8424.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors
@article{tauszig_toll-related_2000,
title = {Toll-related receptors and the control of antimicrobial peptide expression in Drosophila},
author = {Servane Tauszig and Emmanuelle Jouanguy and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1073/pnas.180130797},
issn = {0027-8424},
year = {2000},
date = {2000-09-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {97},
number = {19},
pages = {10520--10525},
abstract = {Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides. Drosophila has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler. Two of these genes, Toll-3 and Toll-4, are expressed at a low level. Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions. Finally, Toll-5 is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.},
keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Hoffmann Jules A
Signaling mechanisms in the antimicrobial host defense of Drosophila Journal Article
In: Current Opinion in Microbiology, vol. 3, no. 1, pp. 16–22, 2000, ISSN: 1369-5274.
Abstract | BibTeX | Tags: Animals, Anti-Infective Agents, Cell Surface, Gene Expression Regulation, Genes, hoffmann, imler, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptors
@article{imler_signaling_2000,
title = {Signaling mechanisms in the antimicrobial host defense of Drosophila},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {1369-5274},
year = {2000},
date = {2000-02-01},
journal = {Current Opinion in Microbiology},
volume = {3},
number = {1},
pages = {16--22},
abstract = {Drosophila has appeared in recent years as a powerful model to study innate immunity. Several papers published in the past year shed light on the role of the three Rel proteins Dorsal, Dif and Relish in the regulation of antimicrobial peptide expression. In addition, the discovery that a blood serine protease inhibitor is involved in the control of the antifungal response indicates that Toll is activated upon triggering of a proteolytic cascade and does not function as a Drosophila pattern recognition receptor.},
keywords = {Animals, Anti-Infective Agents, Cell Surface, Gene Expression Regulation, Genes, hoffmann, imler, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Tauszig Servane, Jouanguy Emmanuelle, Forestier C, Hoffmann Jules A
LPS-induced immune response in Drosophila Journal Article
In: Journal of Endotoxin Research, vol. 6, no. 6, pp. 459–462, 2000, ISSN: 0968-0519.
Abstract | BibTeX | Tags: Animals, Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, hoffmann, imler, Insect, Insect Proteins, Lipopolysaccharides, M3i, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors
@article{imler_lps-induced_2000,
title = {LPS-induced immune response in Drosophila},
author = {Jean-Luc Imler and Servane Tauszig and Emmanuelle Jouanguy and C Forestier and Jules A Hoffmann},
issn = {0968-0519},
year = {2000},
date = {2000-01-01},
journal = {Journal of Endotoxin Research},
volume = {6},
number = {6},
pages = {459--462},
abstract = {The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.},
keywords = {Animals, Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, hoffmann, imler, Insect, Insect Proteins, Lipopolysaccharides, M3i, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
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}
}
1999
Levashina Elena A, Langley E, Green C, Gubb David, Ashburner M, Hoffmann Jules A, Reichhart Jean-Marc
Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila Journal Article
In: Science, vol. 285, no. 5435, pp. 1917–1919, 1999, ISSN: 0036-8075.
Abstract | BibTeX | Tags: Animals, Antifungal Agents, Antimicrobial Cationic Peptides, Body Patterning, Cell Surface, Escherichia coli, Genes, Hemolymph, hoffmann, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutagenesis, Peptides, Receptors, Recombinant Fusion Proteins, reichhart, Serine Proteinase Inhibitors, Serpins, Signal Transduction, Toll-Like Receptors, Up-Regulation
@article{levashina_constitutive_1999,
title = {Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila},
author = {Elena A Levashina and E Langley and C Green and David Gubb and M Ashburner and Jules A Hoffmann and Jean-Marc Reichhart},
issn = {0036-8075},
year = {1999},
date = {1999-09-01},
journal = {Science},
volume = {285},
number = {5435},
pages = {1917--1919},
abstract = {The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.},
keywords = {Animals, Antifungal Agents, Antimicrobial Cationic Peptides, Body Patterning, Cell Surface, Escherichia coli, Genes, Hemolymph, hoffmann, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutagenesis, Peptides, Receptors, Recombinant Fusion Proteins, reichhart, Serine Proteinase Inhibitors, Serpins, Signal Transduction, Toll-Like Receptors, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
Manfruelli P, Reichhart Jean-Marc, Steward R, Hoffmann Jules A, Lemaitre Bruno
A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF Journal Article
In: EMBO J., vol. 18, no. 12, pp. 3380–3391, 1999, ISSN: 0261-4189.
Abstract | Links | BibTeX | Tags: Animals, Anti-Infective Agents, Cell Surface, Clone Cells, DNA-Binding Proteins, Fat Body, Female, Gene Expression Regulation, Genes, hoffmann, Insect, Insect Proteins, Larva, M3i, Male, Membrane Glycoproteins, Mosaicism, Mutation, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Reporter, Signal Transduction, Toll-Like Receptors, Transcription Factors
@article{manfruelli_mosaic_1999,
title = {A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF},
author = {P Manfruelli and Jean-Marc Reichhart and R Steward and Jules A Hoffmann and Bruno Lemaitre},
doi = {10.1093/emboj/18.12.3380},
issn = {0261-4189},
year = {1999},
date = {1999-06-01},
journal = {EMBO J.},
volume = {18},
number = {12},
pages = {3380--3391},
abstract = {Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--textgreater Toll--textgreaterCactus--textgreaterDorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.},
keywords = {Animals, Anti-Infective Agents, Cell Surface, Clone Cells, DNA-Binding Proteins, Fat Body, Female, Gene Expression Regulation, Genes, hoffmann, Insect, Insect Proteins, Larva, M3i, Male, Membrane Glycoproteins, Mosaicism, Mutation, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Reporter, Signal Transduction, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
1998
Ferrandon Dominique, Jung Alain C, Criqui M, Lemaitre Bruno, Uttenweiler-Joseph S, Michaut Lydia, Reichhart Jean-Marc, Hoffmann Jules A
A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway Journal Article
In: EMBO J., vol. 17, no. 5, pp. 1217–1227, 1998, ISSN: 0261-4189.
Abstract | Links | BibTeX | Tags: Animals, bacteria, Cell Surface, Developmental, Digestive System, Epithelium, Fat Body, Female, ferrandon, Fungal, Gene Expression Regulation, Genes, Green Fluorescent Proteins, hoffmann, Insect Proteins, Larva, Luminescent Proteins, M3i, Male, Membrane Glycoproteins, Organ Specificity, Receptors, reichhart, Reporter, Respiratory System, Spores, Toll-Like Receptors, Trachea, Transgenes
@article{ferrandon_drosomycin-gfp_1998,
title = {A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway},
author = {Dominique Ferrandon and Alain C Jung and M Criqui and Bruno Lemaitre and S Uttenweiler-Joseph and Lydia Michaut and Jean-Marc Reichhart and Jules A Hoffmann},
doi = {10.1093/emboj/17.5.1217},
issn = {0261-4189},
year = {1998},
date = {1998-08-01},
journal = {EMBO J.},
volume = {17},
number = {5},
pages = {1217--1227},
abstract = {A hallmark of the systemic antimicrobial response of Drosophila is the synthesis by the fat body of several antimicrobial peptides which are released into the hemolymph in response to a septic injury. One of these peptides, drosomycin, is active primarily against fungi. Using a drosomycin-green fluorescent protein (GFP) reporter gene, we now show that in addition to the fat body, a variety of epithelial tissues that are in direct contact with the external environment, including those of the respiratory, digestive and reproductive tracts, can express the antifungal peptide, suggesting a local response to infections affecting these barrier tissues. As is the case for vertebrate epithelia, insect epithelia appear to be more than passive physical barriers and are likely to constitute an active component of innate immunity. We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway.},
keywords = {Animals, bacteria, Cell Surface, Developmental, Digestive System, Epithelium, Fat Body, Female, ferrandon, Fungal, Gene Expression Regulation, Genes, Green Fluorescent Proteins, hoffmann, Insect Proteins, Larva, Luminescent Proteins, M3i, Male, Membrane Glycoproteins, Organ Specificity, Receptors, reichhart, Reporter, Respiratory System, Spores, Toll-Like Receptors, Trachea, Transgenes},
pubstate = {published},
tppubtype = {article}
}
Nicolas E, Reichhart Jean-Marc, Hoffmann Jules A, Lemaitre Bruno
In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila Journal Article
In: J. Biol. Chem., vol. 273, no. 17, pp. 10463–10469, 1998, ISSN: 0021-9258.
Abstract | BibTeX | Tags: Animals, Cell Surface, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, Insect Proteins, Larva, M3i, Membrane Glycoproteins, Phosphoproteins, Proto-Oncogene Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription Factor RelB, Transcription Factors
@article{nicolas_vivo_1998,
title = {In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila},
author = {E Nicolas and Jean-Marc Reichhart and Jules A Hoffmann and Bruno Lemaitre},
issn = {0021-9258},
year = {1998},
date = {1998-04-01},
journal = {J. Biol. Chem.},
volume = {273},
number = {17},
pages = {10463--10469},
abstract = {The dorsoventral regulatory gene pathway (spätzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila. This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals. Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response. We observe that the cactus gene is up-regulated in response to immune challenge. Interestingly, the expression of the cactus gene is controlled by the spätzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated. We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge. This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response.},
keywords = {Animals, Cell Surface, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, Insect Proteins, Larva, M3i, Membrane Glycoproteins, Phosphoproteins, Proto-Oncogene Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription Factor RelB, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
1996
Lemaitre Bruno, Nicolas E, Michaut Lydia, Reichhart Jean-Marc, Hoffmann Jules A
The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults Journal Article
In: Cell, vol. 86, no. 6, pp. 973–983, 1996, ISSN: 0092-8674.
Abstract | BibTeX | Tags: Animals, Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors
@article{lemaitre_dorsoventral_1996,
title = {The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults},
author = {Bruno Lemaitre and E Nicolas and Lydia Michaut and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0092-8674},
year = {1996},
date = {1996-01-01},
journal = {Cell},
volume = {86},
number = {6},
pages = {973--983},
abstract = {The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.},
keywords = {Animals, Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
1995
Lemaitre Bruno, Meister Marie, Govind S, Georgel Philippe, Steward R, Reichhart Jean-Marc, Hoffmann Jules A
Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila Journal Article
In: EMBO J., vol. 14, no. 3, pp. 536–545, 1995, ISSN: 0261-4189.
Abstract | BibTeX | Tags: Animals, Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biological Transport, Cell Nucleus, Cell Surface, DNA-Binding Proteins, Fat Body, Gene Expression Regulation, Genetic, hoffmann, Immunity, Immunohistochemistry, Insect Hormones, Insect Proteins, M3i, Melanins, Membrane Glycoproteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription, Transcription Factors
@article{lemaitre_functional_1995,
title = {Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila},
author = {Bruno Lemaitre and Marie Meister and S Govind and Philippe Georgel and R Steward and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0261-4189},
year = {1995},
date = {1995-01-01},
journal = {EMBO J.},
volume = {14},
number = {3},
pages = {536--545},
abstract = {In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury. Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells. Here we present data which strongly suggest that the nuclear localization of dl during the immune response is controlled by the Toll signaling pathway, comprising gene products that participate in the intracellular part of the embryonic dorsoventral pathway. We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear. Together, these results point to a potential link between the Toll signaling pathway and melanotic tumor induction. Although dl has been shown previously to bind to kappa B-related motifs within the promoter of the antibacterial peptide coding gene diptericin, we find that injury-induced expression of diptericin can occur in the absence of dl. Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent. These data underline the complexity of the Drosophila immune response. Finally, we observed that like other rel proteins, dl can control the level of its own transcription.},
keywords = {Animals, Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biological Transport, Cell Nucleus, Cell Surface, DNA-Binding Proteins, Fat Body, Gene Expression Regulation, Genetic, hoffmann, Immunity, Immunohistochemistry, Insect Hormones, Insect Proteins, M3i, Melanins, Membrane Glycoproteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}