Schaeffer Evelyne, Sánchez-Fernández Elena M, Gonçalves-Pereira Rita, Flacher Vincent, Lamon Delphine, Duval Monique, Fauny Jean-Daniel, Fernández José M García, Mueller Christopher G, Mellet Carmen Ortiz
In: European Journal of Medicinal Chemistry, vol. 169, pp. 111–120, 2019, ISSN: 1768-3254.
Abstract | Links | BibTeX | Tags: Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller
@article{schaeffer_sp2-iminosugar_2019,
title = {sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo},
author = {Evelyne Schaeffer and Elena M Sánchez-Fernández and Rita Gonçalves-Pereira and Vincent Flacher and Delphine Lamon and Monique Duval and Jean-Daniel Fauny and José M García Fernández and Christopher G Mueller and Carmen Ortiz Mellet},
doi = {10.1016/j.ejmech.2019.02.078},
issn = {1768-3254},
year = {2019},
date = {2019-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {169},
pages = {111--120},
abstract = {Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling.},
keywords = {Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller},
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}
}
Romani N, Flacher V, Tripp C H, Sparber F, Ebner S, Stoitzner P
Targeting skin dendritic cells to improve intradermal vaccination Journal Article
In: Current Topics in Microbiology and Immunology, vol. 351, pp. 113–138, 2012, ISSN: 0070-217X.
Abstract | Links | BibTeX | Tags: Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases
@article{romani_targeting_2012,
title = {Targeting skin dendritic cells to improve intradermal vaccination},
author = {N Romani and V Flacher and C H Tripp and F Sparber and S Ebner and P Stoitzner},
doi = {10.1007/82_2010_118},
issn = {0070-217X},
year = {2012},
date = {2012-01-01},
journal = {Current Topics in Microbiology and Immunology},
volume = {351},
pages = {113--138},
abstract = {Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(neg), and dermal langerin(+) dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin(neg) dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14(+) dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge.},
keywords = {Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases},
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: 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}
}
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}
}
Durand Stéphanie H, Flacher Vincent, Roméas Annick, Carrouel Florence, Colomb Evelyne, Vincent Claude, Magloire Henry, Couble Marie-Lise, Bleicher Françoise, Staquet Marie-Jeanne, Lebecque Serge, Farges Jean-Christophe
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 176, no. 5, pp. 2880–2887, 2006, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation
@article{durand_lipoteichoic_2006,
title = {Lipoteichoic acid increases TLR and functional chemokine expression while reducing dentin formation in in vitro differentiated human odontoblasts},
author = {Stéphanie H Durand and Vincent Flacher and Annick Roméas and Florence Carrouel and Evelyne Colomb and Claude Vincent and Henry Magloire and Marie-Lise Couble and Françoise Bleicher and Marie-Jeanne Staquet and Serge Lebecque and Jean-Christophe Farges},
doi = {10.4049/jimmunol.176.5.2880},
issn = {0022-1767},
year = {2006},
date = {2006-03-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {176},
number = {5},
pages = {2880--2887},
abstract = {Gram-positive bacteria entering the dentinal tissue during the carious process are suspected to influence the immune response in human dental pulp. Odontoblasts situated at the pulp/dentin interface are the first cells encountered by these bacteria and therefore could play a crucial role in this response. In the present study, we found that in vitro-differentiated odontoblasts constitutively expressed the pattern recognition receptor TLR1-6 and 9 genes but not TLR7, 8, and 10. Furthermore, lipoteichoic acid (LTA), a wall component of Gram-positive bacteria, triggered the activation of the odontoblasts. LTA up-regulated the expression of its own receptor TLR2, as well as the production of several chemokines. In particular, an increased amount of CCL2 and CXCL10 was detected in supernatants from LTA-stimulated odontoblasts, and those supernatants augmented the migration of immature dendritic cells in vitro compared with controls. Clinical relevance of these observations came from immunohistochemical analysis showing that CCL2 was expressed in vivo by odontoblasts and blood vessels present under active carious lesions but not in healthy dental pulps. In contrast with this inflammatory response, gene expression of major dentin matrix components (type I collagen, dentin sialophosphoprotein) and TGF-beta1 was sharply down-regulated in odontoblasts by LTA. Taken together, these data suggest that odontoblasts activated through TLR2 by Gram-positive bacteria LTA are able to initiate an innate immune response by secreting chemokines that recruit immature dendritic cells while down-regulating their specialized functions of dentin matrix synthesis and mineralization.},
keywords = {Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}