Publications
2019
Vargas-Franco Jorge William, Castaneda Beatriz, Gama Andrea, Mueller Christopher G, Heymann Dominique, Rédini Françoise, Lézot Frédéric
In: Biochemical Pharmacology, vol. 168, pp. 133–148, 2019, ISSN: 1873-2968.
Abstract | Links | BibTeX | Tags: Animals, Bone Density Conservation Agents, Bone Development, Craniofacial bone, Gene Knockout Techniques, Growth, Inbred C57BL, Knockout, Long bone, Mice, Newborn, Osteoprotegerin, RANK ligand, RANKL/RANK/OPG, Skull, Team-Mueller, Tibia, Tooth, X-Ray Microtomography, Zoledronic acid
@article{vargas-franco_genetically-achieved_2019,
title = {Genetically-achieved disturbances to the expression levels of TNFSF11 receptors modulate the effects of zoledronic acid on growing mouse skeletons},
author = {Jorge William Vargas-Franco and Beatriz Castaneda and Andrea Gama and Christopher G Mueller and Dominique Heymann and Françoise Rédini and Frédéric Lézot},
doi = {10.1016/j.bcp.2019.06.027},
issn = {1873-2968},
year = {2019},
date = {2019-10-01},
journal = {Biochemical Pharmacology},
volume = {168},
pages = {133--148},
abstract = {Zoledronic acid (ZOL), a nitrogen bisphosphonate (N-BP), is currently used to treat and control pediatric osteolytic diseases. Variations in the intensity of the effects and side effects of N-BPs have been reported with no clear explanations regarding their origins. We wonder if such variations could be associated with different levels of RANKL signaling activity in growing bone during and after the treatment with N-BPs. To answer this question, ZOL was injected into neonate C57BL/6J mice with different genetically-determined RANKL signaling activity levels (Opg+/+textbackslashRankTg-, Opg+/+textbackslashRankTg+, Opg+/-textbackslashRankTg-, Opg+/-textbackslashRankTg+, Opg-/-textbackslashRankTg- and Opg-/-textbackslashRankTg+ mice) following a protocol (4 injections from post-natal day 1 to 7 at the dose of 50 μg/kg) that mimics those used in onco-pediatric patients. At the end of pediatric growth (1 and half months) and at an adult age (10 months), the bone morphometric and mineral parameters were measured using μCT in the tibia and skull for the different mice. A histologic analysis of the dental and periodontal tissues was also performed. At the end of pediatric growth, a delay in long bone and skull bone growth, a blockage of tooth eruption, some molar root alterations and a neoplasia-like structure associated with incisor development were found. Interestingly, the magnitude of these side effects was reduced by Opg deficiency (Opg-/-) but increased by Rank overexpression (RankTg). Analysis of the skeletal phenotype at ten months confirmed respectively the beneficial and harmful effects of Opg deficiency and Rank overexpression. These results validated the hypothesis that the RANKL signaling activity level in the bone microenvironment is implicated in the modulation of the response to ZOL. Further studies will be necessary to understand the underlying molecular mechanisms, which will help decipher the variability in the effects of N-BPs reported in the human population. SIGNIFICANT STATEMENTS: The present study establishes that in mice the RANKL signaling activity level is a major modulator of the effects and side-effects of bisphosphonates on the individual skeleton during growth. However, the modulatory actions are dependent on the ways in which this level of activity is increased. A decrease in OPG expression is beneficial to the skeletal phenotype observed at the end of growth, while RANK overexpression deteriorates it. Far removed from pediatric treatment, in adults, the skeletal phenotypes initially observed at the end of growth for the different levels of RANKL signaling activity were maintained, although significant improvement was associated only with reductions in OPG expression.},
keywords = {Animals, Bone Density Conservation Agents, Bone Development, Craniofacial bone, Gene Knockout Techniques, Growth, Inbred C57BL, Knockout, Long bone, Mice, Newborn, Osteoprotegerin, RANK ligand, RANKL/RANK/OPG, Skull, Team-Mueller, Tibia, Tooth, X-Ray Microtomography, Zoledronic acid},
pubstate = {published},
tppubtype = {article}
}
2015
Mairhofer David G, Ortner Daniela, Tripp Christoph H, Schaffenrath Sandra, Fleming Viktor, Heger Lukas, Komenda Kerstin, Reider Daniela, Dudziak Diana, Chen Suzie, Becker Jürgen C, Flacher Vincent, Stoitzner Patrizia
Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model Journal Article
In: The Journal of Investigative Dermatology, vol. 135, no. 11, pp. 2785–2793, 2015, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity
@article{mairhofer_impaired_2015,
title = {Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model},
author = {David G Mairhofer and Daniela Ortner and Christoph H Tripp and Sandra Schaffenrath and Viktor Fleming and Lukas Heger and Kerstin Komenda and Daniela Reider and Diana Dudziak and Suzie Chen and Jürgen C Becker and Vincent Flacher and Patrizia Stoitzner},
doi = {10.1038/jid.2015.241},
issn = {1523-1747},
year = {2015},
date = {2015-11-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {11},
pages = {2785--2793},
abstract = {Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.},
keywords = {Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity},
pubstate = {published},
tppubtype = {article}
}
2012
Hess E, Duheron V, Decossas M, Lezot F, Berdal A, Chea S, Golub R, Bosisio M R, Bridal S L, Choi Y, Yagita H, Mueller C G
RANKL induces organized lymph node growth by stromal cell proliferation Journal Article
In: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), pp. 1245–1254, 2012.
Abstract | Links | BibTeX | Tags: Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Proliferation, Chemokine CCL19, Chemokine CXCL13, chemokines, CXCL13, cytology, development, Growth, growth & development, Hair, hair follicle, Homeostasis, Human, Immune System, Immunization, ligand, LYMPH, LYMPH NODE, Lymph Nodes, Mice, mouse, physiology, plasticity, Proliferation, Protein, rank, RANK ligand, Regulation, Secondary, Stromal Cells, Team-Mueller, transgenic, VCAM1
@article{hess_rankl_2012,
title = {RANKL induces organized lymph node growth by stromal cell proliferation},
author = {E Hess and V Duheron and M Decossas and F Lezot and A Berdal and S Chea and R Golub and M R Bosisio and S L Bridal and Y Choi and H Yagita and C G Mueller},
doi = {10.4049/jimmunol.1101513},
year = {2012},
date = {2012-01-01},
journal = {Journal of Immunology},
volume = {188},
number = {1550-6606 (Electronic)},
pages = {1245--1254},
abstract = {RANK and its ligand RANKL play important roles in the development and regulation of the immune system. We show that mice transgenic for Rank in hair follicles display massive postnatal growth of skin-draining lymph nodes. The proportions of hematopoietic and nonhematopoietic stromal cells and their organization are maintained, with the exception of an increase in B cell follicles. The hematopoietic cells are not activated and respond to immunization by foreign Ag and adjuvant. We demonstrate that soluble RANKL is overproduced from the transgenic hair follicles and that its neutralization normalizes lymph node size, inclusive area, and numbers of B cell follicles. Reticular fibroblastic and vascular stromal cells, important for secondary lymphoid organ formation and organization, express RANK and undergo hyperproliferation, which is abrogated by RANKL neutralization. In addition, they express higher levels of CXCL13 and CCL19 chemokines, as well as MAdCAM-1 and VCAM-1 cell-adhesion molecules. These findings highlight the importance of tissue-derived cues for secondary lymphoid organ homeostasis and identify RANKL as a key molecule for controlling the plasticity of the immune system},
keywords = {Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Proliferation, Chemokine CCL19, Chemokine CXCL13, chemokines, CXCL13, cytology, development, Growth, growth & development, Hair, hair follicle, Homeostasis, Human, Immune System, Immunization, ligand, LYMPH, LYMPH NODE, Lymph Nodes, Mice, mouse, physiology, plasticity, Proliferation, Protein, rank, RANK ligand, Regulation, Secondary, Stromal Cells, Team-Mueller, transgenic, VCAM1},
pubstate = {published},
tppubtype = {article}
}
2011
Duheron V, Hess E, Duval M, Decossas M, Castaneda B, Klopper J E, Amoasii L, Barbaroux J B, Williams I R, Yagita H, Penninger J, Choi Y, Lezot F, Groves R, Paus R, Mueller C G
Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit Journal Article
In: Proc.Natl.Acad.Sci.U.S.A, vol. 108, no. 1091-6490 (Electronic), pp. 5342–5347, 2011.
Abstract | Links | BibTeX | Tags: Activation, Animals, Cell Proliferation, Chemistry, cytology, Epidermis, Epithelial Cells, function, Genetics, Growth, Hair, hair follicle, Homeostasis, Immunology, Inbred C57BL, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, Nude, Osteoprotegerin, physiology, Proliferation, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, signaling, Skin, Skin Transplantation, stem, Stem Cells, Team-Mueller, transgenic, TRANSGENIC MICE, TRANSPLANTATION
@article{duheron_receptor_2011,
title = {Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit},
author = {V Duheron and E Hess and M Duval and M Decossas and B Castaneda and J E Klopper and L Amoasii and J B Barbaroux and I R Williams and H Yagita and J Penninger and Y Choi and F Lezot and R Groves and R Paus and C G Mueller},
doi = {10.1073/pnas.1013054108},
year = {2011},
date = {2011-03-01},
journal = {Proc.Natl.Acad.Sci.U.S.A},
volume = {108},
number = {1091-6490 (Electronic)},
pages = {5342--5347},
abstract = {Receptor activator of NF-kappaB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermo-pilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities},
keywords = {Activation, Animals, Cell Proliferation, Chemistry, cytology, Epidermis, Epithelial Cells, function, Genetics, Growth, Hair, hair follicle, Homeostasis, Immunology, Inbred C57BL, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, Nude, Osteoprotegerin, physiology, Proliferation, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, signaling, Skin, Skin Transplantation, stem, Stem Cells, Team-Mueller, transgenic, TRANSGENIC MICE, TRANSPLANTATION},
pubstate = {published},
tppubtype = {article}
}
2010
Noordegraaf Madelon, Flacher Vincent, Stoitzner Patrizia, Clausen Björn E
Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity Journal Article
In: The Journal of Investigative Dermatology, vol. 130, no. 12, pp. 2752–2759, 2010, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: Animal, Animals, Antigen, Antigens, C-Type, CHS, contact, CONTACT HYPERSENSITIVITY, Dendritic Cells, DEPLETION, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, Diphtheria Toxin, Disease Models, Epidermis, function, Gene Knock-In Techniques, Genetics, Growth, HAPTEN, Haptens, Heparin-binding EGF-like Growth Factor, Hypersensitivity, Immunology, Inbred C57BL, INDUCTION, Intercellular Signaling Peptides and Proteins, LACKING, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Mannose-Binding Lectins, metabolism, Mice, mouse, Mutant Strains, Organ Culture Techniques, pathology, Peptides, Poisons, Protein, Proteins, RESPONSES, signaling, Skin, Surface, Team-Mueller, Toxicity
@article{noordegraaf_functional_2010,
title = {Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity},
author = {Madelon Noordegraaf and Vincent Flacher and Patrizia Stoitzner and Björn E Clausen},
doi = {10.1038/jid.2010.223},
issn = {1523-1747},
year = {2010},
date = {2010-12-01},
journal = {The Journal of Investigative Dermatology},
volume = {130},
number = {12},
pages = {2752--2759},
abstract = {The relative roles of Langerhans cells (LC), dermal dendritic cells (DC), and, in particular, the recently discovered Langerin(+) dermal DC subset in the induction and control of contact hypersensitivity (CHS) responses remain controversial. Using an inducible mouse model, in which LC and other Langerin(+) DC can be depleted by injection of diphtheria toxin, we previously reported impaired transport of topically applied antigen to draining lymph nodes and reduced CHS in the absence of all Langerin(+) skin DC. In this study, we demonstrate that mice with a selective depletion of LC exhibit attenuated CHS only upon sensitization with a low hapten dose but not with a high hapten dose. In contrast, when painting a higher concentration of hapten onto the skin, which leads to increased antigen dissemination into the dermis, CHS is still diminished in mice lacking all Langerin(+) skin DC. Taken together, these data suggest that the magnitude of a CHS reaction depends on the number of skin DC, which have access to the hapten, rather than on the presence or absence of a particular skin DC population. LC and (Langerin(+)) dermal DC thus seem to have a redundant function in regulating CHS.},
keywords = {Animal, Animals, Antigen, Antigens, C-Type, CHS, contact, CONTACT HYPERSENSITIVITY, Dendritic Cells, DEPLETION, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, Diphtheria Toxin, Disease Models, Epidermis, function, Gene Knock-In Techniques, Genetics, Growth, HAPTEN, Haptens, Heparin-binding EGF-like Growth Factor, Hypersensitivity, Immunology, Inbred C57BL, INDUCTION, Intercellular Signaling Peptides and Proteins, LACKING, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Mannose-Binding Lectins, metabolism, Mice, mouse, Mutant Strains, Organ Culture Techniques, pathology, Peptides, Poisons, Protein, Proteins, RESPONSES, signaling, Skin, Surface, Team-Mueller, Toxicity},
pubstate = {published},
tppubtype = {article}
}
2009
Flacher Vincent, Sparber Florian, Tripp Christoph H, Romani Nikolaus, Stoitzner Patrizia
Targeting of epidermal Langerhans cells with antigenic proteins: attempts to harness their properties for immunotherapy Journal Article
In: Cancer immunology, immunotherapy: CII, vol. 58, no. 7, pp. 1137–1147, 2009, ISSN: 1432-0851.
Abstract | Links | BibTeX | Tags: Active, Animals, Antibodies, antibody, Antigen, Antigens, BLOOD, C-Type, cancer, CD, CD4-Positive T-Lymphocytes, CD4+ T cells, CD8-Positive T-Lymphocytes, CD8+ T cells, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Growth, Human, Humans, immune response, IMMUNE-RESPONSES, Immunization, Immunology, Immunotherapy, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Major Histocompatibility Complex, Mannose-Binding Lectins, metabolism, methods, MHC class I, MHC class I molecules, Mice, Neoplasm, Neoplasms, OVALBUMIN, Patients, PROGENITORS, Protein, Proteins, RESPONSES, review, Skin, T CELLS, T-CELLS, Team-Mueller, therapy, tumor
@article{flacher_targeting_2009,
title = {Targeting of epidermal Langerhans cells with antigenic proteins: attempts to harness their properties for immunotherapy},
author = {Vincent Flacher and Florian Sparber and Christoph H Tripp and Nikolaus Romani and Patrizia Stoitzner},
doi = {10.1007/s00262-008-0563-9},
issn = {1432-0851},
year = {2009},
date = {2009-07-01},
journal = {Cancer immunology, immunotherapy: CII},
volume = {58},
number = {7},
pages = {1137--1147},
abstract = {Langerhans cells, a subset of skin dendritic cells in the epidermis, survey peripheral tissue for invading pathogens. In recent functional studies it was proven that Langerhans cells can present exogenous antigen not merely on major histocompatibility complexes (MHC)-class II molecules to CD4+ T cells, but also on MHC-class I molecules to CD8+ T cells. Immune responses against topically applied antigen could be measured in skin-draining lymph nodes. Skin barrier disruption or co-application of adjuvants was required for maximal induction of T cell responses. Cytotoxic T cells induced by topically applied antigen inhibited tumor growth in vivo, thus underlining the potential of Langerhans cells for immunotherapy. Here we review recent work and report novel observations relating to the potential use of Langerhans cells for immunotherapy. We investigated the potential of epicutaneous immunization strategies in which resident skin dendritic cells are loaded with tumor antigen in situ. This contrasts with current clinical approaches, where dendritic cells generated from progenitors in blood are loaded with tumor antigen ex vivo before injection into cancer patients. In the current study, we applied either fluorescently labeled protein antigen or targeting antibodies against DEC-205/CD205 and langerin/CD207 topically onto barrier-disrupted skin and examined antigen capture and transport by Langerhans cells. Protein antigen could be detected in Langerhans cells in situ, and they were the main skin dendritic cell subset transporting antigen during emigration from skin explants. Potent in vivo proliferative responses of CD4+ and CD8+ T cells were measured after epicutaneous immunization with low amounts of protein antigen. Targeting antibodies were mainly transported by langerin+ migratory dendritic cells of which the majority represented migratory Langerhans cells and a smaller subset the new langerin+ dermal dendritic cell population located in the upper dermis. The preferential capture of topically applied antigen by Langerhans cells and their ability to induce potent CD4+ and CD8+ T cell responses emphasizes their potential for epicutaneous immunization strategies.},
keywords = {Active, Animals, Antibodies, antibody, Antigen, Antigens, BLOOD, C-Type, cancer, CD, CD4-Positive T-Lymphocytes, CD4+ T cells, CD8-Positive T-Lymphocytes, CD8+ T cells, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Growth, Human, Humans, immune response, IMMUNE-RESPONSES, Immunization, Immunology, Immunotherapy, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Major Histocompatibility Complex, Mannose-Binding Lectins, metabolism, methods, MHC class I, MHC class I molecules, Mice, Neoplasm, Neoplasms, OVALBUMIN, Patients, PROGENITORS, Protein, Proteins, RESPONSES, review, Skin, T CELLS, T-CELLS, Team-Mueller, therapy, tumor},
pubstate = {published},
tppubtype = {article}
}
2008
Kwan Wing-Hong, Navarro-Sanchez Erika, Dumortier Hélène, Decossas Marion, Vachon Hortense, dos Santos Flavia Barreto, Fridman Hervé W, Rey Félix A, Harris Eva, Despres Philippe, Mueller Christopher G
Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth Journal Article
In: PLoS neglected tropical diseases, vol. 2, no. 10, pp. e311, 2008, ISSN: 1935-2735.
Abstract | Links | BibTeX | Tags: Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus
@article{kwan_dermal-type_2008b,
title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},
author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},
doi = {10.1371/journal.pntd.0000311},
issn = {1935-2735},
year = {2008},
date = {2008-10-01},
journal = {PLoS neglected tropical diseases},
volume = {2},
number = {10},
pages = {e311},
abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection.
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},
keywords = {Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus},
pubstate = {published},
tppubtype = {article}
}
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.
2004
Martineau Y., Bec C. Le, Monbrun L., Allo V., Chiu I. M., Danos O., Moine H., Prats H., Prats A. C.
Internal ribosome entry site structural motifs conserved among mammalian fibroblast growth factor 1 alternatively spliced mRNAs Journal Article
In: Mol Cell Biol, vol. 24, no. 17, pp. 7622-35, 2004, (0270-7306 Journal Article).
Abstract | BibTeX | Tags: (Genetics), *5', *Alternative, *Nucleic, *Promoter, 1/*genetics, Acid, Alignment, Animals, Base, Cell, Conformation, Data, EHRESMANN, Factor, Fibroblast, Gene, Genes, Genetic, Gov't, Growth, Human, Line, Messenger/chemistry/*genetics/metabolism, Mice, Molecular, Muscle, Mutagenesis, Non-U.S., Regions, Ribosomes/*metabolism, RNA, Sequence, Site-Directed, Skeletal/cytology/physiology, Splicing, Structural/genetics, Support, Techniques, Transfer, Untranslated, Vectors
@article{,
title = {Internal ribosome entry site structural motifs conserved among mammalian fibroblast growth factor 1 alternatively spliced mRNAs},
author = { Y. Martineau and C. Le Bec and L. Monbrun and V. Allo and I. M. Chiu and O. Danos and H. Moine and H. Prats and A. C. Prats},
year = {2004},
date = {2004-01-01},
journal = {Mol Cell Biol},
volume = {24},
number = {17},
pages = {7622-35},
abstract = {Fibroblast growth factor 1 (FGF-1) is a powerful angiogenic factor whose gene structure contains four promoters, giving rise to a process of alternative splicing resulting in four mRNAs with alternative 5' untranslated regions (5' UTRs). Here we have identified, by using double luciferase bicistronic vectors, the presence of internal ribosome entry sites (IRESs) in the human FGF-1 5' UTRs, particularly in leaders A and C, with distinct activities in mammalian cells. DNA electrotransfer in mouse muscle revealed that the IRES present in the FGF-1 leader A has a high activity in vivo. We have developed a new regulatable TET OFF bicistronic system, which allowed us to rule out the possibility of any cryptic promoter in the FGF-1 leaders. FGF-1 IRESs A and C, which were mapped in fragments of 118 and 103 nucleotides, respectively, are flexible in regard to the position of the initiation codon, making them interesting from a biotechnological point of view. Furthermore, we show that FGF-1 IRESs A of murine and human origins show similar IRES activity profiles. Enzymatic and chemical probing of the FGF-1 IRES A RNA revealed a structural domain conserved among mammals at both the nucleotide sequence and RNA structure levels. The functional role of this structural motif has been demonstrated by point mutagenesis, including compensatory mutations. These data favor an important role of IRESs in the control of FGF-1 expression and provide a new IRES structural motif that could help IRES prediction in 5' UTR databases.},
note = {0270-7306
Journal Article},
keywords = {(Genetics), *5', *Alternative, *Nucleic, *Promoter, 1/*genetics, Acid, Alignment, Animals, Base, Cell, Conformation, Data, EHRESMANN, Factor, Fibroblast, Gene, Genes, Genetic, Gov't, Growth, Human, Line, Messenger/chemistry/*genetics/metabolism, Mice, Molecular, Muscle, Mutagenesis, Non-U.S., Regions, Ribosomes/*metabolism, RNA, Sequence, Site-Directed, Skeletal/cytology/physiology, Splicing, Structural/genetics, Support, Techniques, Transfer, Untranslated, Vectors},
pubstate = {published},
tppubtype = {article}
}
2003
Bonnal S., Schaeffer C., Creancier L., Clamens S., Moine H., Prats A. C., Vagner S.
A single internal ribosome entry site containing a G quartet RNA structure drives fibroblast growth factor 2 gene expression at four alternative translation initiation codons Journal Article
In: J Biol Chem, vol. 278, no. 41, pp. 39330-6, 2003, (0021-9258 Journal Article).
Abstract | BibTeX | Tags: 2/*genetics, Acid, Alternative, Base, Cell, Chain, Codon, Complementary/genetics, Conformation, Data, Deletion, DNA, Expression, Factor, Fibroblast, Gene, Gov't, Growth, Human, initiation, Initiator/genetics, Line, Messenger/*chemistry/*genetics, Molecular, Non-U.S., Nucleic, Peptide, Ribosomes/*metabolism, RNA, Sequence, Splicing, Support, Transfection
@article{,
title = {A single internal ribosome entry site containing a G quartet RNA structure drives fibroblast growth factor 2 gene expression at four alternative translation initiation codons},
author = { S. Bonnal and C. Schaeffer and L. Creancier and S. Clamens and H. Moine and A. C. Prats and S. Vagner},
year = {2003},
date = {2003-01-01},
journal = {J Biol Chem},
volume = {278},
number = {41},
pages = {39330-6},
abstract = {The 484-nucleotide (nt) alternatively translated region (ATR) of the human fibroblast growth factor 2 (FGF-2) mRNA contains four CUG and one AUG translation initiation codons. Although the 5'-end proximal CUG codon is initiated by a cap-dependent translation process, the other four initiation codons are initiated by a mechanism of internal entry of ribosomes. We undertook here a detailed analysis of the cis-acting elements defining the FGF-2 internal ribosome entry site (IRES). A thorough deletion analysis study within the 5'-ATR led us to define a 176-nt region as being necessary and sufficient for IRES function at four codons present in a downstream 308-nt RNA segment. Unexpectedly, a single IRES module is therefore responsible for translation initiation at four distantly localized codons. The determination of the FGF-2 5'-ATR RNA secondary structure by enzymatic and chemical probing experiments showed that the FGF-2 IRES contained two stem-loop regions and a G quartet motif that constitute novel structural determinants of IRES function.},
note = {0021-9258
Journal Article},
keywords = {2/*genetics, Acid, Alternative, Base, Cell, Chain, Codon, Complementary/genetics, Conformation, Data, Deletion, DNA, Expression, Factor, Fibroblast, Gene, Gov't, Growth, Human, initiation, Initiator/genetics, Line, Messenger/*chemistry/*genetics, Molecular, Non-U.S., Nucleic, Peptide, Ribosomes/*metabolism, RNA, Sequence, Splicing, Support, Transfection},
pubstate = {published},
tppubtype = {article}
}