Publications
2020
Mueller Christopher G, Camara Abdouramane, Flacher Vincent
[The sinusoidal microenvironment regulates the niche and the differentiation of lymph node macrophages] Journal Article
In: Medecine Sciences: M/S, vol. 36, no. 10, pp. 835–838, 2020, ISSN: 1958-5381.
Links | BibTeX | Tags: Animals, Capillaries, Cell Differentiation, Cellular, Humans, Immunity, Lymph Nodes, Lymphatic Vessels, Macrophages, Stem Cell Niche, Team-Mueller
@article{mueller_sinusoidal_2020,
title = {[The sinusoidal microenvironment regulates the niche and the differentiation of lymph node macrophages]},
author = {Christopher G Mueller and Abdouramane Camara and Vincent Flacher},
doi = {10.1051/medsci/2020148},
issn = {1958-5381},
year = {2020},
date = {2020-01-01},
journal = {Medecine Sciences: M/S},
volume = {36},
number = {10},
pages = {835--838},
keywords = {Animals, Capillaries, Cell Differentiation, Cellular, Humans, Immunity, Lymph Nodes, Lymphatic Vessels, Macrophages, Stem Cell Niche, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
2019
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}
}
2016
Chypre M, Seaman J, Cordeiro O G, Willen L, Knoop K A, Buchanan A, Sainson R C, Williams I R, Yagita H, Schneider P, Mueller C G
Characterization and application of two RANK-specific antibodies with different biological activities Journal Article
In: Immunol.Lett., vol. 171, no. 1879-0542 (Electronic), pp. 5–14, 2016.
Abstract | Links | BibTeX | Tags: Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy
@article{chypre_characterization_2016,
title = {Characterization and application of two RANK-specific antibodies with different biological activities},
author = {M Chypre and J Seaman and O G Cordeiro and L Willen and K A Knoop and A Buchanan and R C Sainson and I R Williams and H Yagita and P Schneider and C G Mueller},
doi = {10.1016/j.imlet.2016.01.003},
year = {2016},
date = {2016-03-01},
journal = {Immunol.Lett.},
volume = {171},
number = {1879-0542 (Electronic)},
pages = {5--14},
abstract = {Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-kappaB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-kappaB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools},
keywords = {Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy},
pubstate = {published},
tppubtype = {article}
}
Dietrich Damien, Martin Praxedis, Flacher Vincent, Sun Yu, Jarrossay David, Brembilla Nicolo, Mueller Christopher, Arnett Heather A, Palmer Gaby, Towne Jennifer, Gabay Cem
Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines Journal Article
In: Cytokine, vol. 84, pp. 88–98, 2016, ISSN: 1096-0023.
Abstract | Links | BibTeX | Tags: agonists, ANTAGONIST, BLOOD, Cells, Cellular, Chemistry, Cultured, cytokine, CYTOKINE PRODUCTION, Cytokines, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, IL-1, IL-1R1, IL-1ra, IL-36, IL-36R, Immunoassay, Immunology, immunopathology, inflammation, Interleukin, Interleukin-1 Receptor Accessory Protein, Interleukin-1 Type I, KERATINOCYTES, Langerhans Cells, Macrophage, Macrophages, messenger, Molecular Biology, Monocytes, mRNA, Myeloid Cells, pathology, Phenotype, PRODUCTION, PROINFLAMMATORY CYTOKINES, Receptor, receptor antagonist, Receptors, RNA, signaling, Skin, target, Team-Mueller, TONSIL
@article{dietrich_interleukin-36_2016,
title = {Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines},
author = {Damien Dietrich and Praxedis Martin and Vincent Flacher and Yu Sun and David Jarrossay and Nicolo Brembilla and Christopher Mueller and Heather A Arnett and Gaby Palmer and Jennifer Towne and Cem Gabay},
doi = {10.1016/j.cyto.2016.05.012},
issn = {1096-0023},
year = {2016},
date = {2016-01-01},
journal = {Cytokine},
volume = {84},
pages = {88--98},
abstract = {Interleukin (IL)-36 cytokines belong to the IL-1 family and include three agonists, IL-36 α, β and γ and one inhibitor, IL-36 receptor antagonist (IL-36Ra). IL-36 and IL-1 (α and β) activate similar intracellular pathways via their related heterodimeric receptors, IL-36R/IL-1RAcP and IL-1R1/IL-1RAcP, respectively. However, excessive IL-36 versus IL-1 signaling induces different phenotypes in humans, which may be related to differential expression of their respective receptors. We examined the expression of IL-36R, IL-1R1 and IL-1RAcP mRNA in human peripheral blood, tonsil and skin immune cells by RT-qPCR. Monocyte-derived dendritic cells (MDDC), M0, M1 or M2-polarized macrophages, primary keratinocytes, dermal macrophages and Langerhans cells (LC) were stimulated with IL-1β or IL-36β. Cytokine production was assessed by RT-qPCR and immunoassays. The highest levels of IL-36R mRNA were found in skin-derived keratinocytes, LC, dermal macrophages and dermal CD1a(+) DC. In the blood and in tonsils, IL-36R mRNA was predominantly found in myeloid cells. By contrast, IL-1R1 mRNA was detected in almost all cell types with higher levels in tonsil and skin compared to peripheral blood immune cells. IL-36β was as potent as IL-1β in stimulating M2 macrophages, keratinocytes and LC, less potent than IL-1β in stimulating M0 macrophages and MDDC, and exerted no effects in M1 and dermal macrophages. Levels of IL-1Ra diminished the ability of M2 macrophages to respond to IL-1. Taken together, these data are consistent with the association of excessive IL-36 signaling with an inflammatory skin phenotype and identify human LC and M2 macrophages as new IL-36 target cells.},
keywords = {agonists, ANTAGONIST, BLOOD, Cells, Cellular, Chemistry, Cultured, cytokine, CYTOKINE PRODUCTION, Cytokines, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, IL-1, IL-1R1, IL-1ra, IL-36, IL-36R, Immunoassay, Immunology, immunopathology, inflammation, Interleukin, Interleukin-1 Receptor Accessory Protein, Interleukin-1 Type I, KERATINOCYTES, Langerhans Cells, Macrophage, Macrophages, messenger, Molecular Biology, Monocytes, mRNA, Myeloid Cells, pathology, Phenotype, PRODUCTION, PROINFLAMMATORY CYTOKINES, Receptor, receptor antagonist, Receptors, RNA, signaling, Skin, target, Team-Mueller, TONSIL},
pubstate = {published},
tppubtype = {article}
}
2014
Flacher Vincent, Tripp Christoph H, Mairhofer David G, Steinman Ralph M, Stoitzner Patrizia, Idoyaga Juliana, Romani Nikolaus
Murine Langerin+ dermal dendritic cells prime CD8+ Ŧ cells while Langerhans cells induce cross-tolerance Journal Article
In: EMBO molecular medicine, vol. 6, no. 9, pp. 1191–1204, 2014, ISSN: 1757-4684.
Abstract | Links | BibTeX | Tags: agonists, Animals, Antibodies, antibody, Antigen, Antigen Presentation, Antigens, C-Type, C-type lectin, cancer, CD70, CD8-Positive T-Lymphocytes, CD8+ T cells, CD8+ T‐cell responses, Cellular, CROSS-PRESENTATION, Cross-Priming, Cytotoxicity, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, disease, imiquimod, Immunization, IMMUNOGENICITY, Immunologic Memory, Immunological, Immunology, In vivo, Inbred C57BL, INDUCTION, Intradermal, Langerhans Cells, LECTIN, Lectins, Mannose-Binding Lectins, Maturation, Mice, Models, murine, OVALBUMIN, physiology, priming, RESPONSES, Skin, Surface, T CELLS, T-CELLS, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines
@article{flacher_murine_2014,
title = {Murine Langerin+ dermal dendritic cells prime CD8+ Ŧ cells while Langerhans cells induce cross-tolerance},
author = {Vincent Flacher and Christoph H Tripp and David G Mairhofer and Ralph M Steinman and Patrizia Stoitzner and Juliana Idoyaga and Nikolaus Romani},
doi = {10.15252/emmm.201303283},
issn = {1757-4684},
year = {2014},
date = {2014-09-01},
journal = {EMBO molecular medicine},
volume = {6},
number = {9},
pages = {1191--1204},
abstract = {Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8(+) T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin(+) dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin(+) dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8(+) T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8(+) T cells. Langerin/OVA combined with imiquimod could not prime CD8(+) T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin(+) dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8(+) T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.},
keywords = {agonists, Animals, Antibodies, antibody, Antigen, Antigen Presentation, Antigens, C-Type, C-type lectin, cancer, CD70, CD8-Positive T-Lymphocytes, CD8+ T cells, CD8+ T‐cell responses, Cellular, CROSS-PRESENTATION, Cross-Priming, Cytotoxicity, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, disease, imiquimod, Immunization, IMMUNOGENICITY, Immunologic Memory, Immunological, Immunology, In vivo, Inbred C57BL, INDUCTION, Intradermal, Langerhans Cells, LECTIN, Lectins, Mannose-Binding Lectins, Maturation, Mice, Models, murine, OVALBUMIN, physiology, priming, RESPONSES, Skin, Surface, T CELLS, T-CELLS, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}
2011
Limmer Stefanie, Haller Samantha, Drenkard Eliana, Lee Janice, Yu Shen, Kocks Christine, Ausubel Frederick M, Ferrandon Dominique
Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model Journal Article
In: Proc. Natl. Acad. Sci. U.S.A., vol. 108, no. 42, pp. 17378–17383, 2011, ISSN: 1091-6490.
Abstract | Links | BibTeX | Tags: Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence
@article{limmer_pseudomonas_2011b,
title = {Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model},
author = {Stefanie Limmer and Samantha Haller and Eliana Drenkard and Janice Lee and Shen Yu and Christine Kocks and Frederick M Ausubel and Dominique Ferrandon},
doi = {10.1073/pnas.1114907108},
issn = {1091-6490},
year = {2011},
date = {2011-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {108},
number = {42},
pages = {17378--17383},
abstract = {An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.},
keywords = {Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence},
pubstate = {published},
tppubtype = {article}
}
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}
}
2006
Gottar Marie, Gobert Vanessa, Matskevich Alexey A, Reichhart Jean-Marc, Wang Chengshu, Butt Tariq M, Belvin Marcia, Hoffmann Jules A, Ferrandon Dominique
Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors Journal Article
In: Cell, vol. 127, no. 7, pp. 1425–1437, 2006, ISSN: 0092-8674.
Abstract | Links | BibTeX | Tags: Animals, Antibody Formation, Beauveria, Candida albicans, Carrier Proteins, Cellular, ferrandon, Glucans, hoffmann, Immunity, Immunological, M3i, Metarhizium, Models, Polysaccharides, reichhart, Serine Endopeptidases, Signal Transduction, Virulence Factors
@article{gottar_dual_2006,
title = {Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors},
author = {Marie Gottar and Vanessa Gobert and Alexey A Matskevich and Jean-Marc Reichhart and Chengshu Wang and Tariq M Butt and Marcia Belvin and Jules A Hoffmann and Dominique Ferrandon},
doi = {10.1016/j.cell.2006.10.046},
issn = {0092-8674},
year = {2006},
date = {2006-12-01},
journal = {Cell},
volume = {127},
number = {7},
pages = {1425--1437},
abstract = {The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host.},
keywords = {Animals, Antibody Formation, Beauveria, Candida albicans, Carrier Proteins, Cellular, ferrandon, Glucans, hoffmann, Immunity, Immunological, M3i, Metarhizium, Models, Polysaccharides, reichhart, Serine Endopeptidases, Signal Transduction, Virulence Factors},
pubstate = {published},
tppubtype = {article}
}
1997
Dimarcq Jean-Luc, Imler Jean-Luc, Lanot R, Ezekowitz Alan R B, Hoffmann Jules A, Janeway C A, Lagueux Marie
Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression Journal Article
In: Insect Biochemistry and Molecular Biology, vol. 27, no. 10, pp. 877–886, 1997, ISSN: 0965-1748.
Abstract | BibTeX | Tags: Animals, Bacterial Infections, Cellular, Ecdysone, Gene Expression, Genes, Hemocytes, Hemolymph, hoffmann, imler, Immunity, Insect, M3i, Macrophages, Peptide Biosynthesis, Phagocytosis
@article{dimarcq_treatment_1997,
title = {Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression},
author = {Jean-Luc Dimarcq and Jean-Luc Imler and R Lanot and Alan R B Ezekowitz and Jules A Hoffmann and C A Janeway and Marie Lagueux},
issn = {0965-1748},
year = {1997},
date = {1997-10-01},
journal = {Insect Biochemistry and Molecular Biology},
volume = {27},
number = {10},
pages = {877--886},
abstract = {Insects rely on both humoral and cellular mechanisms to defend themselves against microbial infections. The humoral response involves synthesis of a battery of potent antimicrobial peptides by the fat body and, to a lesser extent, by blood cells. The cellular response on the other hand consists of phagocytosis of small microorganisms and melanization and encapsulation of larger parasites. The l(2)mbn cell line, established from tumorous larval hemocytes, represents a system of choice to dissect the molecular events controlling cellular immunity. We report here that l(2)mbn cells can be efficiently induced to differentiate in adherent, macrophage-like cells by treatment with 20-hydroxyecdysone. Ecdysone treatment increases both the phagocytic capacity of l(2)mbn cells and their competence to express antimicrobial genes in response to immune challenge. We also report that expression of several regulatory molecules thought to be involved in the immune response is up-regulated by ecdysone in l(2)mbn cells.},
keywords = {Animals, Bacterial Infections, Cellular, Ecdysone, Gene Expression, Genes, Hemocytes, Hemolymph, hoffmann, imler, Immunity, Insect, M3i, Macrophages, Peptide Biosynthesis, Phagocytosis},
pubstate = {published},
tppubtype = {article}
}
1995
Hoffmann Jules A
Innate immunity of insects Journal Article
In: Curr. Opin. Immunol., vol. 7, no. 1, pp. 4–10, 1995, ISSN: 0952-7915.
Abstract | BibTeX | Tags: Animals, Anti-Bacterial Agents, Blood Proteins, Cellular, Defensins, Gene Expression Regulation, hoffmann, Immunity, Innate, insects, M3i, Peptides
@article{hoffmann_innate_1995,
title = {Innate immunity of insects},
author = {Jules A Hoffmann},
issn = {0952-7915},
year = {1995},
date = {1995-02-01},
journal = {Curr. Opin. Immunol.},
volume = {7},
number = {1},
pages = {4--10},
abstract = {Insects are particularly resistant to microorganisms. Their host-defense system relies on several innate reactions: upon injury, the immediate onset of two proteolytic cascades leading to localized blood clotting and to melanization, the latter process involving production of cytotoxic molecules (namely reactive oxygen intermediates); the phagocytosis of bacteria and the encapsulation of larger parasites by blood cells; the induced synthesis by the fat body of a battery of potent antimicrobial peptides/polypeptides which are secreted into the hemolymph where they act synergistically to kill the invading microorganisms. The insect host defence system shares many of the basic characteristics of the mammalian acute phase response, especially at the level of the coordinate control of gene expression, where similar cis-regulatory and inducible transactivators appear to play key functions. The powerful techniques developed to study the genetics of Drosophila provide a unique opportunity to dissect the development and differentiation of this primordial immune system and may contribute to our understanding of the innate immune response in higher organisms.},
keywords = {Animals, Anti-Bacterial Agents, Blood Proteins, Cellular, Defensins, Gene Expression Regulation, hoffmann, Immunity, Innate, insects, M3i, Peptides},
pubstate = {published},
tppubtype = {article}
}
1993
Reichhart Jean-Marc, Georgel Philippe, Meister Marie, Lemaitre Bruno, Kappler Christine, Hoffmann Jules A
Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila Journal Article
In: C. R. Acad. Sci. III, Sci. Vie, vol. 316, no. 10, pp. 1218–1224, 1993, ISSN: 0764-4469.
Abstract | BibTeX | Tags: Animals, Blotting, Cellular, Gene Expression, Genes, Genetic, hoffmann, Immunity, Insect, M3i, NF-kappa B, Northern, reichhart, translocation, Zygote
@article{reichhart_expression_1993,
title = {Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila},
author = {Jean-Marc Reichhart and Philippe Georgel and Marie Meister and Bruno Lemaitre and Christine Kappler and Jules A Hoffmann},
issn = {0764-4469},
year = {1993},
date = {1993-01-01},
journal = {C. R. Acad. Sci. III, Sci. Vie},
volume = {316},
number = {10},
pages = {1218--1224},
abstract = {The rel/NF-kappa B-related morphogen dorsal is a maternally expressed gene which is involved in the control of the dorso-ventral axis during early embryogenesis of Drosophila. We show that this gene is also expressed in the fat body of larvae and adults of Drosophila as well as in a tumorous blood cell line: its expression is noticeably enhanced upon bacterial (or lipopolysaccharide) challenge. This challenge also induces within 15-30 min a nuclear translocation of the dorsal protein. The genes encoding inducible antibacterial peptides in Drosophila contain kappa B-related nucleotide sequences and we show that the dorsal protein can bind to such motifs and sequence-specifically transactivate a reporter gene in co-transfection experiments with a Drosophila cell line. However, in dl1 mutants, in the absence of dorsal protein, the genes encoding antibacterial peptides retain their inducibility, suggesting a multifactorial control. The results indicate that in addition to its role in embryogenesis, dorsal is involved in the immune response of Drosophila. They also strengthen the analogy between the mammalian acute phase response and the insect immune response.},
keywords = {Animals, Blotting, Cellular, Gene Expression, Genes, Genetic, hoffmann, Immunity, Insect, M3i, NF-kappa B, Northern, reichhart, translocation, Zygote},
pubstate = {published},
tppubtype = {article}
}
1990
Hoffmann Danièle, Hoffmann Jules A
Cellular and molecular aspects of insect immunity Journal Article
In: Res. Immunol., vol. 141, no. 9, pp. 895–896, 1990, ISSN: 0923-2494.
BibTeX | Tags: Animals, Cellular, hoffmann, Immunity, insects, M3i, Molecular Biology
@article{hoffmann_cellular_1990,
title = {Cellular and molecular aspects of insect immunity},
author = {Danièle Hoffmann and Jules A Hoffmann},
issn = {0923-2494},
year = {1990},
date = {1990-12-01},
journal = {Res. Immunol.},
volume = {141},
number = {9},
pages = {895--896},
keywords = {Animals, Cellular, hoffmann, Immunity, insects, M3i, Molecular Biology},
pubstate = {published},
tppubtype = {article}
}
1977
Brehelin M, Zachary Daniel, Hoffmann Jules A
Comparative study of hemocyte capsule formation in Locusta migratoria, Melolontha melolontha and Calliphora erythrocephala Journal Article
In: Ann Parasitol Hum Comp, vol. 52, no. 1, pp. 66–67, 1977, ISSN: 0003-4150.
BibTeX | Tags: Animals, Beetles, Blood Cells, Cellular, Diptera, Grasshoppers, Hemocytes, hoffmann, Immunity, M3i
@article{brehelin_comparative_1977,
title = {Comparative study of hemocyte capsule formation in Locusta migratoria, Melolontha melolontha and Calliphora erythrocephala},
author = {M Brehelin and Daniel Zachary and Jules A Hoffmann},
issn = {0003-4150},
year = {1977},
date = {1977-02-01},
journal = {Ann Parasitol Hum Comp},
volume = {52},
number = {1},
pages = {66--67},
keywords = {Animals, Beetles, Blood Cells, Cellular, Diptera, Grasshoppers, Hemocytes, hoffmann, Immunity, M3i},
pubstate = {published},
tppubtype = {article}
}
Hoffmann Danièle, Brehelin M, Hoffmann Jules A
First results of the antibacterial defense reactions of Locusta migratoria larva and imago Journal Article
In: Ann Parasitol Hum Comp, vol. 52, no. 1, pp. 87–88, 1977, ISSN: 0003-4150.
BibTeX | Tags: Animals, Bacillus thuringiensis, bacteria, Cellular, Grasshoppers, Hematopoietic System, Hemocytes, Hemolymph, hoffmann, Immunity, Larva, M3i, Muramidase
@article{hoffmann_first_1977,
title = {First results of the antibacterial defense reactions of Locusta migratoria larva and imago},
author = {Danièle Hoffmann and M Brehelin and Jules A Hoffmann},
issn = {0003-4150},
year = {1977},
date = {1977-02-01},
journal = {Ann Parasitol Hum Comp},
volume = {52},
number = {1},
pages = {87--88},
keywords = {Animals, Bacillus thuringiensis, bacteria, Cellular, Grasshoppers, Hematopoietic System, Hemocytes, Hemolymph, hoffmann, Immunity, Larva, M3i, Muramidase},
pubstate = {published},
tppubtype = {article}
}