Camara Abdouramane, Cordeiro Olga G, Alloush Farouk, Sponsel Janina, Chypre Mélanie, Onder Lucas, Asano Kenichi, Tanaka Masato, Yagita Hideo, Ludewig Burkhard, Flacher Vincent, Mueller Christopher G
Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche Journal Article
In: Immunity, vol. 50, no. 6, pp. 1467–1481.e6, 2019, ISSN: 1097-4180.
Abstract | Links | BibTeX | Tags: Activation, Animals, Biomarkers, Cell Differentiation, Cells, Cellular, Cellular Microenvironment, cytokine, Cytokines, deficiency, Differentiation, Endothelial Cells, ENDOTHELIAL-CELLS, environment, Expression, immune regulation, Immunology, Immunophenotyping, inflammation, LYMPH, LYMPH NODE, Lymph Nodes, lymphatic endothelial cells, Lymphoid Tissue, Macrophage, Macrophages, Mesenchymal Stem Cells, mesenchymal stromal cells, Mice, rank, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Regulation, Signal Transduction, Stromal Cells, Team-Mueller, transgenic
@article{camara_lymph_2019,
title = {Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche},
author = {Abdouramane Camara and Olga G Cordeiro and Farouk Alloush and Janina Sponsel and Mélanie Chypre and Lucas Onder and Kenichi Asano and Masato Tanaka and Hideo Yagita and Burkhard Ludewig and Vincent Flacher and Christopher G Mueller},
doi = {10.1016/j.immuni.2019.05.008},
issn = {1097-4180},
year = {2019},
date = {2019-01-01},
journal = {Immunity},
volume = {50},
number = {6},
pages = {1467--1481.e6},
abstract = {Tissue-resident macrophages are receptive to specific signals concentrated in cellular niches that direct their cell differentiation and maintenance genetic programs. Here, we found that deficiency of the cytokine RANKL in lymphoid tissue organizers and marginal reticular stromal cells of lymph nodes resulted in the loss of the CD169+ sinusoidal macrophages (SMs) comprising the subcapsular and the medullary subtypes. Subcapsular SM differentiation was impaired in mice with targeted RANK deficiency in SMs. Temporally controlled RANK removal in lymphatic endothelial cells (LECs) revealed that lymphatic RANK activation during embryogenesis and shortly after birth was required for the differentiation of both SM subtypes. Moreover, RANK expression by LECs was necessary for SM restoration after inflammation-induced cell loss. Thus, cooperation between mesenchymal cells and LECs shapes a niche environment that supports SM differentiation and reconstitution after inflammation.},
keywords = {Activation, Animals, Biomarkers, Cell Differentiation, Cells, Cellular, Cellular Microenvironment, cytokine, Cytokines, deficiency, Differentiation, Endothelial Cells, ENDOTHELIAL-CELLS, environment, Expression, immune regulation, Immunology, Immunophenotyping, inflammation, LYMPH, LYMPH NODE, Lymph Nodes, lymphatic endothelial cells, Lymphoid Tissue, Macrophage, Macrophages, Mesenchymal Stem Cells, mesenchymal stromal cells, Mice, rank, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Regulation, Signal Transduction, Stromal Cells, Team-Mueller, transgenic},
pubstate = {published},
tppubtype = {article}
}
Quintin Jessica, Asmar Joelle, Matskevich Alexey A, Lafarge Marie-Céline, Ferrandon Dominique
The Drosophila Toll pathway controls but does not clear Candida glabrata infections Journal Article
In: J. Immunol., vol. 190, no. 6, pp. 2818–2827, 2013, ISSN: 1550-6606.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Animal, Animals, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, ferrandon, Immunologic, M3i, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence
@article{quintin_drosophila_2013b,
title = {The Drosophila Toll pathway controls but does not clear Candida glabrata infections},
author = {Jessica Quintin and Joelle Asmar and Alexey A Matskevich and Marie-Céline Lafarge and Dominique Ferrandon},
doi = {10.4049/jimmunol.1201861},
issn = {1550-6606},
year = {2013},
date = {2013-03-01},
journal = {J. Immunol.},
volume = {190},
number = {6},
pages = {2818--2827},
abstract = {The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host.},
keywords = {Adaptor Proteins, Animal, Animals, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, ferrandon, Immunologic, M3i, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence},
pubstate = {published},
tppubtype = {article}
}
Ayyaz Arshad, Giammarinaro Philippe, Liégeois Samuel, Lestradet Matthieu, Ferrandon Dominique
In: Immunobiology, vol. 218, no. 4, pp. 635–644, 2013, ISSN: 1878-3279.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors
@article{ayyaz_negative_2013b,
title = {A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus},
author = {Arshad Ayyaz and Philippe Giammarinaro and Samuel Liégeois and Matthieu Lestradet and Dominique Ferrandon},
doi = {10.1016/j.imbio.2012.07.027},
issn = {1878-3279},
year = {2013},
date = {2013-01-01},
journal = {Immunobiology},
volume = {218},
number = {4},
pages = {635--644},
abstract = {Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development.},
keywords = {Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
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}
}
Barbaroux J B, Beleut M, Brisken C, Mueller C G, Groves R W
Epidermal receptor activator of NF-kappaB ligand controls Langerhans cells numbers and proliferation Journal Article
In: Journal of Immunology, vol. 181, no. 1550-6606 (Electronic), pp. 1103–1108, 2008.
Abstract | BibTeX | Tags: APC, Apoptosis, BLOOD, Cell Count, Cell Proliferation, Cell Survival, Culture, cytology, Dendritic Cells, DERMATOLOGY, Differentiation, Epidermis, Expression, Homeostasis, Human, Humans, Immunology, IN VITRO, In vivo, KERATINOCYTES, Langerhans Cells, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, OSTEOCLAST, Osteoclasts, Proliferation, Protein, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Signal Transduction, Skin, survival, Team-Mueller, viability
@article{barbaroux_epidermal_2008,
title = {Epidermal receptor activator of NF-kappaB ligand controls Langerhans cells numbers and proliferation},
author = {J B Barbaroux and M Beleut and C Brisken and C G Mueller and R W Groves},
year = {2008},
date = {2008-01-01},
journal = {Journal of Immunology},
volume = {181},
number = {1550-6606 (Electronic)},
pages = {1103--1108},
abstract = {Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-kappaB ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34(+) progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 +/- 1% vs 55.2 +/- 5.7% live cells, respectively; n = 4; p textless 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 +/- 77.2 vs 873.6 +/- 41.6 LC per mm(2); n = 9; p textless 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis},
keywords = {APC, Apoptosis, BLOOD, Cell Count, Cell Proliferation, Cell Survival, Culture, cytology, Dendritic Cells, DERMATOLOGY, Differentiation, Epidermis, Expression, Homeostasis, Human, Humans, Immunology, IN VITRO, In vivo, KERATINOCYTES, Langerhans Cells, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, OSTEOCLAST, Osteoclasts, Proliferation, Protein, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Signal Transduction, Skin, survival, Team-Mueller, viability},
pubstate = {published},
tppubtype = {article}
}
Kwan W H, Boix C, Gougelet N, Fridman W H, Mueller C G
LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors Journal Article
In: Journal of Leukocyte Biology, vol. 82, no. 0741-5400 (Print), pp. 133–141, 2007.
Abstract | BibTeX | Tags: Activation, APC, Cell Differentiation, COLONY-STIMULATING FACTOR, cytokine, Cytokines, cytology, Dendritic Cells, Differentiation, GM-CSF, Human, Humans, IL-10, IL10, IMMATURE, immune response, Immune Tolerance, Immunity, Immunology, inflammation, interleukin 10, Interleukin-10, lipopolysaccharide, Lipopolysaccharides, LPS, Macrophage, Macrophage Colony-Stimulating Factor, Maturation, metabolism, MODULATION, monocyte, Monocytes, MYCOBACTERIA, Mycobacterium, Myeloid Cells, Pharmacology, precursor, PRODUCTION, Protein, Receptor, Secondary, T CELL ACTIVATION, Team-Mueller
@article{kwan_lps_2007,
title = {LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors},
author = {W H Kwan and C Boix and N Gougelet and W H Fridman and C G Mueller},
year = {2007},
date = {2007-07-01},
journal = {Journal of Leukocyte Biology},
volume = {82},
number = {0741-5400 (Print)},
pages = {133--141},
abstract = {Dendritic cells (DC) obtained by culturing myeloid precursors in GM-CSF undergo maturation and induce an efficient T cell response when stimulated with microbial products. DC precursors themselves also recognize microbial products, and it remains unclear how these stimulated DC precursors modulate the immune response. We show here that M-CSF-conditioned human DC precursors responded to LPS, Mycobacteria bovis, and inflammatory cytokines by a rapid and robust production of IL-10, largely superior to that observed with immature DC or monocytes. The endogenous IL-10 restrained the DC precursors from converting into professional APC, as blocking the IL-10 receptor in the presence of LPS resulted in the formation of efficient T cell stimulators. LPS stimulation concomitant with DC differentiation gave rise to immature DC, which were tolerant to a secondary LPS exposure. Furthermore, the LPS-activated DC precursors reduced bystander DC maturation and anti-CD3/CD28-triggered T cell activation. These data suggest that when exposed to inflammatory or microbial signals, M-CSF-conditioned DC precursors can participate in the modulation of inflammation and immune response by rapid release of IL-10},
keywords = {Activation, APC, Cell Differentiation, COLONY-STIMULATING FACTOR, cytokine, Cytokines, cytology, Dendritic Cells, Differentiation, GM-CSF, Human, Humans, IL-10, IL10, IMMATURE, immune response, Immune Tolerance, Immunity, Immunology, inflammation, interleukin 10, Interleukin-10, lipopolysaccharide, Lipopolysaccharides, LPS, Macrophage, Macrophage Colony-Stimulating Factor, Maturation, metabolism, MODULATION, monocyte, Monocytes, MYCOBACTERIA, Mycobacterium, Myeloid Cells, Pharmacology, precursor, PRODUCTION, Protein, Receptor, Secondary, T CELL ACTIVATION, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Mueller C G, Boix C, Kwan W H, Daussy C, Fournier E, Fridman W H, Molina T J
Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation Journal Article
In: Journal of Leukocyte Biology, vol. 82, no. 0741-5400 (Print), pp. 567–575, 2007.
Abstract | BibTeX | Tags: Activation, Antigen, Antigens, B CELL ACTIVATION, B CELLS, B-Cell, B-Cell Activation Factor Receptor, B-Lymphocytes, Biological, BLOOD, CC, CD14, CD40, Cell Division, Cell Proliferation, Cell Survival, Chemokine CCL5, chemokines, Coculture, cytology, Dendritic Cells, Differentiation, Diffuse, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Human, Humans, IL-2, Immunoenzyme Techniques, Interleukin-2, Large B-Cell, Lymph Nodes, LYMPHOMA, metabolism, monocyte, Monocytes, Myeloid Cells, pathology, Proliferation, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, survival, Team-Mueller, tumor, Tumor Markers
@article{mueller_critical_2007,
title = {Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation},
author = {C G Mueller and C Boix and W H Kwan and C Daussy and E Fournier and W H Fridman and T J Molina},
year = {2007},
date = {2007-01-01},
journal = {Journal of Leukocyte Biology},
volume = {82},
number = {0741-5400 (Print)},
pages = {567--575},
abstract = {Large B cell lymphomas can comprise numerous CD14+ cells in the tumor stroma, which raises the question of whether monocytes can support B cell survival and proliferation. We show that the coculture of monocytes with B cells from peripheral blood or from diffuse large B cell lymphoma enabled prolonged B cell survival. Under these conditions, diffuse large lymphoma B cells proliferated, and addition of B cell-activating factor of the TNF family (BAFF) and IL-2 enhanced cell division. Monocytes and dendritic cells (DC) had similar antiapoptotic activity on healthy B cells but displayed differences with respect to B cell proliferation. Monocytes and cord blood-derived CD14+ cells promoted B cell proliferation in the presence of an anti-CD40 stimulus, whereas DC supported B cell proliferation when activated through the BCR. DC and CD14+ cells were able to induce plasmocyte differentiation. When B cells were activated via the BCR or CD40, they released the leukocyte attractant CCL5, and this chemokine is one of the main chemokines expressed in diffuse large B cell lymphoma. The data support the notion that large B cell lymphoma recruit monocytes via CCL5 to support B cell survival and proliferation},
keywords = {Activation, Antigen, Antigens, B CELL ACTIVATION, B CELLS, B-Cell, B-Cell Activation Factor Receptor, B-Lymphocytes, Biological, BLOOD, CC, CD14, CD40, Cell Division, Cell Proliferation, Cell Survival, Chemokine CCL5, chemokines, Coculture, cytology, Dendritic Cells, Differentiation, Diffuse, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Human, Humans, IL-2, Immunoenzyme Techniques, Interleukin-2, Large B-Cell, Lymph Nodes, LYMPHOMA, metabolism, monocyte, Monocytes, Myeloid Cells, pathology, Proliferation, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, survival, Team-Mueller, tumor, Tumor Markers},
pubstate = {published},
tppubtype = {article}
}
Chen Li-Ying, Wang Juinn-Chin, Hyvert Yann, Lin Hui-Ping, Perrimon Norbert, Imler Jean-Luc, Hsu Jui-Chou
Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo Journal Article
In: Current biology: CB, vol. 16, no. 12, pp. 1183–1193, 2006, ISSN: 0960-9822.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers
@article{chen_weckle_2006,
title = {Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo},
author = {Li-Ying Chen and Juinn-Chin Wang and Yann Hyvert and Hui-Ping Lin and Norbert Perrimon and Jean-Luc Imler and Jui-Chou Hsu},
doi = {10.1016/j.cub.2006.05.050},
issn = {0960-9822},
year = {2006},
date = {2006-06-01},
journal = {Current biology: CB},
volume = {16},
number = {12},
pages = {1183--1193},
abstract = {BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.},
keywords = {Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
Marmey B, Boix C, Barbaroux J B, Dieu-Nosjean M C, Diebold J, Audouin J, Fridman W H, Mueller C G, Molina T J
CD14 and CD169 expression in human lymph nodes and spleen: specific expansion of CD14+C Journal Article
In: Hum.Pathol., vol. 37, no. 0046-8177 (Print), pp. 68–77, 2006.
Abstract | BibTeX | Tags: Adhesion, Antigen, Antigens, B-Cell, Biological, CD14, Cell Differentiation, CELL SEPARATION, Dendritic Cells, Differentiation, Diffuse, Direct, Expression, Flow Cytometry, Fluorescent Antibody Technique, Gene, GLYCOPROTEIN, Glycoproteins, granulocyte/macrophage-colony, Human, Humans, Immunoenzyme Techniques, Immunohistochemistry, Immunologic, Large B-Cell, leukemia, LYMPH, LYMPH NODE, Lymph Nodes, Lymphadenitis, Lymphoid Tissue, LYMPHOMA, Macrophage, Macrophages, Membrane, Membrane Glycoproteins, metabolism, Monocytes, pathology, Phagocytosis, Receptor, Receptors, SIALOADHESIN, SPLEEN, Team-Mueller, tumor, Tumor Markers
@article{marmey_cd14_2006,
title = {CD14 and CD169 expression in human lymph nodes and spleen: specific expansion of CD14+C},
author = {B Marmey and C Boix and J B Barbaroux and M C Dieu-Nosjean and J Diebold and J Audouin and W H Fridman and C G Mueller and T J Molina},
year = {2006},
date = {2006-01-01},
journal = {Hum.Pathol.},
volume = {37},
number = {0046-8177 (Print)},
pages = {68--77},
abstract = {The mononuclear phagocyte system of human lymphoid tissue comprises macrophages and dendritic cells (DCs). The heterogeneity of the non-DC mononuclear phagocyte population in human lymphoid tissue has been little addressed. Here, we studied the expression of 2 monocyte-derived markers, CD14 and CD169 (sialoadhesin), in reactive human lymphoid tissue as well as in a series of 51 B-cell lymphomas by immunohistochemistry on paraffin-embedded tissue. We confirmed that lymph node sinusoidal monocyte-derived cells were the only population staining for CD169. Although most sinusoidal histiocytes also expressed CD14, monocyte-derived cells with phagocytosis such as erythrophagocytosis, anthracosis, or tingible bodies macrophage lacked CD14 and CD169. Among B-cell lymphomas, splenic marginal zone lymphoma was the only one associated with an expansion of the CD14(+)CD169(+) cells in the cords. With respect to nodal B-cell lymphomas, CD14(+) cells were rare among B-chronic lymphocytic leukemia, follicular lymphoma (FL), mantle cell lymphoma (MCL). However, strikingly, we found a strong expansion of CD14(+)CD169(-) cells in numerous diffuse large B-cell lymphomas (DLBCLs), except in cases associated with numerous mitoses, apoptotic bodies, and tingible bodies macrophages. When cultivated in granulocyte/macrophage colony stimulating factor/interleukin 4, DLBCL purified CD14(+) cells differentiate into plasmacytoid cells, expressing DC-specific intercellular adhesion molecule 3-grabbing nonintegrin, suggesting dendritic cell differentiation potential. Our observation fits well with the lymph node and host response cluster signatures described in the gene profiling signatures of DLBCL. However, the role of this CD14(+) population that may constitute a microenvironment-related marker of this subgroup of DLBCL remains to be determined},
keywords = {Adhesion, Antigen, Antigens, B-Cell, Biological, CD14, Cell Differentiation, CELL SEPARATION, Dendritic Cells, Differentiation, Diffuse, Direct, Expression, Flow Cytometry, Fluorescent Antibody Technique, Gene, GLYCOPROTEIN, Glycoproteins, granulocyte/macrophage-colony, Human, Humans, Immunoenzyme Techniques, Immunohistochemistry, Immunologic, Large B-Cell, leukemia, LYMPH, LYMPH NODE, Lymph Nodes, Lymphadenitis, Lymphoid Tissue, LYMPHOMA, Macrophage, Macrophages, Membrane, Membrane Glycoproteins, metabolism, Monocytes, pathology, Phagocytosis, Receptor, Receptors, SIALOADHESIN, SPLEEN, Team-Mueller, tumor, Tumor Markers},
pubstate = {published},
tppubtype = {article}
}
Kwan Wing-Hong, Helt Anna-Marija, Marañón Concepción, Barbaroux Jean-Baptiste, Hosmalin Anne, Harris Eva, Fridman Wolf H, Mueller Chris G F
Dendritic cell precursors are permissive to dengue virus and human immunodeficiency virus infection Journal Article
In: Journal of Virology, vol. 79, no. 12, pp. 7291–7299, 2005, ISSN: 0022-538X.
Abstract | Links | BibTeX | Tags: ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, APC, BLOOD, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, COLONY-STIMULATING FACTOR, Cultured, Dendritic Cells, Dengue virus, Differentiation, Epidermis, Hematopoietic Stem Cells, HIV, HIV-1, Human, Humans, IMMATURE, immunodeficiency, infection, interleukin 10, Interleukin-10, Lipopolysaccharide Receptors, MEMORY T CELLS, monocyte, Monocytes, Necrosis, precursor, PROGENITORS, Skin, T CELLS, Team-Mueller, tumor, Tumor Necrosis Factor, viral Infection, virus
@article{kwan_dendritic_2005,
title = {Dendritic cell precursors are permissive to dengue virus and human immunodeficiency virus infection},
author = {Wing-Hong Kwan and Anna-Marija Helt and Concepción Marañón and Jean-Baptiste Barbaroux and Anne Hosmalin and Eva Harris and Wolf H Fridman and Chris G F Mueller},
doi = {10.1128/JVI.79.12.7291-7299.2005},
issn = {0022-538X},
year = {2005},
date = {2005-06-01},
journal = {Journal of Virology},
volume = {79},
number = {12},
pages = {7291--7299},
abstract = {CD14(+) interstitial cells reside beneath the epidermis of skin and mucosal tissue and may therefore play an important role in viral infections and the shaping of an antiviral immune response. However, in contrast to dendritic cells (DC) or blood monocytes, these antigen-presenting cells (APC) have not been well studied. We have previously described long-lived CD14(+) cells generated from CD34(+) hematopoietic progenitors, which may represent model cells for interstitial CD14(+) APC. Here, we show that these cells carry DC-SIGN and differentiate into immature DC in the presence of granulocyte-macrophage colony-stimulating factor. We have compared the CD14(+) cells and the DC derived from these cells with respect to dengue virus and human immunodeficiency virus type 1 (HIV-1) infection. Both cell types are permissive to dengue virus infection, but the CD14(+) cells secrete the anti-inflammatory cytokine interleukin 10 and no tumor necrosis factor alpha. Regarding HIV, the CD14(+) cells are permissive to HIV-1, release higher p24 levels than the derived DC, and more efficiently activate HIV Pol-specific CD8(+) memory T cells. The CD14(+) DC precursors infected with either virus retain their DC differentiation potential. The results suggest that interstitial CD14(+) APC may contribute to HIV-1 and dengue virus infection and the shaping of an antiviral immune response.},
keywords = {ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, APC, BLOOD, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, COLONY-STIMULATING FACTOR, Cultured, Dendritic Cells, Dengue virus, Differentiation, Epidermis, Hematopoietic Stem Cells, HIV, HIV-1, Human, Humans, IMMATURE, immunodeficiency, infection, interleukin 10, Interleukin-10, Lipopolysaccharide Receptors, MEMORY T CELLS, monocyte, Monocytes, Necrosis, precursor, PROGENITORS, Skin, T CELLS, Team-Mueller, tumor, Tumor Necrosis Factor, viral Infection, virus},
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}
}
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 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}
}