RNA interference and receptors

@article{nokey,

title = {CD169(+) macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling},

author = {A. Camara and A. C. Lavanant and J. Abe and H. L. Desforges and Y. O. Alexandre and E. Girardi and Z. Igamberdieva and K. Asano and M. Tanaka and T. Hehlgans and K. Pfeffer and S. Pfeffer and S. N. Mueller and J. V. Stein and C. G. Mueller},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=35031565},

isbn = {35031565},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {119},

number = {3},

pages = {e2108540119},

abstract = {CD169(+) macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169(+) macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTbeta) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTbetaR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTbetaR revealed that both receptors contribute equally to LN CD169(+) macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8(+) T cells. Taken together, the data provide evidence that CD169(+) macrophage differentiation in LN and spleen requires dual signals from LTbetaR and RANK with implications for the immune response.},

note = {1091-6490 (Electronic) 

0027-8424 (Linking) 

Journal Article},

keywords = {PFEFFER, Team-Mueller, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Chikungunya virus envelope protein E2 provides a targeting vector for antigen delivery to human dermal CD14+ dendritic cells},

author = { Brulefert and Kraemer and Cumin and Selle and Hoste and Gad and Rühl and Madinier and Chaloin and Münz and Després and MUELLER and Flacher},

doi = {10.1016/j.jid.2021.04.027},

year  = {2021},

date = {2021-12-01},

journal = {J. Invest. Dermatol},

volume = {141},

number = {12},

pages = {2985-2989},

keywords = {Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Current clinical and pre-clinical imaging approaches to study the cancer-associated immune system},

author = {Mueller and Gaiddon and Venkatasamy},

doi = {doi: 10.3389/fimmu.2021.716860},

year  = {2021},

date = {2021-09-01},

journal = {Frontiers in Immunology},

keywords = {Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{muller_tridimensional_2021,

title = {[Tridimensional in vitro models of nervous and immune systems in the skin]},

author = {Quentin Muller and François Berthod and Vincent Flacher},

doi = {10.1051/medsci/2020260},

issn = {1958-5381},

year  = {2021},

date = {2021-01-01},

journal = {Medecine Sciences: M/S},

volume = {37},

number = {1},

pages = {68--76},

abstract = {The immune system and the sensory nervous system are responsible for perceiving danger under distinct yet complementary forms. In the last few years, neuroimmune interactions have become an important topic of dermatological research for conditions including wound healing, atopic dermatitis and psoriasis. We present here a selection of tridimensional in vitro models that reproduce skin structure and integrate an immune or a sensory function. Future evolutions of such models are expected to greatly contribute in a better understanding of reciprocal influences between sensory nervous system and immune system.},

keywords = {Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{madel:hal-03064977,

title = {Osteoclasts contribute to early development of chronic inflammation by promoting dysregulated hematopoiesis and myeloid skewing},

author = {Maria-Bernadette Madel and Lidia Ibanez and Thomas Ciucci and Julia Halper and Majlinda Topi and Henri-Jean Garchon and Matthieu Rouleau and Christopher Georges Mueller and Laurent Peyrin Biroulet and David Moulin and Claudine Blin-Wakkach and Abdelilah Wakkach},

url = {https://hal.archives-ouvertes.fr/hal-03064977},

doi = {10.1101/2020.12.09.418137},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

note = {working paper or preprint},

keywords = {Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{spenle_tenascin-c_2020,

title = {Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma},

author = {Caroline Spenlé and Thomas Loustau and Devadarssen Murdamoothoo and William Erne and Stephanie Beghelli-de la Forest Divonne and Romain Veber and Luciana Petti and Pierre Bourdely and Matthias Mörgelin and Eva-Maria Brauchle and Gérard Cremel and Vony Randrianarisoa and Abdouramane Camara and Samah Rekima and Sebastian Schaub and Kelly Nouhen and Thomas Imhof and Uwe Hansen and Nicodème Paul and Raphael Carapito and Nicolas Pythoud and Aurélie Hirschler and Christine Carapito and Hélène Dumortier and Christopher G Mueller and Manuel Koch and Katja Schenke-Layland and Shigeyuki Kon and Anne Sudaka and Fabienne Anjuère and Ellen Van Obberghen-Schilling and Gertraud Orend},

doi = {10.1158/2326-6066.CIR-20-0074},

issn = {2326-6074},

year  = {2020},

date = {2020-09-01},

journal = {Cancer Immunology Research},

volume = {8},

number = {9},

pages = {1122--1138},

abstract = {Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c+ myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin α9β1 and binding to CCL21, tenascin-C immobilized CD11c+ cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C-instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.},

keywords = {Dumortier, I2CT, Team-Dumortier, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{jacoberger-foissac_liposomes_2020,

title = {Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists},

author = {Célia Jacoberger-Foissac and Hanadi Saliba and May Wantz and Cendrine Seguin and Vincent Flacher and Benoît Frisch and Béatrice Heurtault and Sylvie Fournel},

doi = {10.1016/j.ejpb.2020.05.026},

issn = {1873-3441},

year  = {2020},

date = {2020-07-01},

journal = {European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik e.V},

volume = {152},

pages = {348--357},

abstract = {Liposomes are powerful tools for the optimization of peptides and adjuvant composition in cancer vaccines. Here, we take advantage of a liposomal platform versatility to develop three vaccine candidates associating a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant. Liposomal vaccine containing MPLA (TLR4 liposomes), are the most effective treatment against the HPV-transformed orthotopic lung tumor mouse model, TC-1. This vaccine induces a potent Th1-oriented antitumor immunity, which leads to a significant reduction in tumor growth and a prolonged survival of mice, even when injected after tumor appearance. This efficacy is dependent on CD8+ T cells. Subcutaneous injection of this treatment induces the migration of skin DCs to draining lymph nodes. Interestingly, TLR2/6 liposomes trigger a weaker Th1-immune response which is not sufficient for the induction of a prolonged antitumor activity. Although NOD1 liposome treatment results in the control of early tumor growth, it does not extend mice survival. Surprisingly, the antitumor activity of NOD1 vaccine is not associated with a specific adaptive immune response. This study shows that our modulable platform can be used for the strategical development of vaccines.},

keywords = {Delivery system, HPV-transformed pulmonary tumors, Liposomal nanoparticles, Team-Mueller, Therapeutic vaccines, Toll-like and nod-like receptor agonists},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{brulefert_vitamin_2020,

title = {Vitamin D3-elicited CD14+ human skin dendritic cells promote thymic stromal lymphopoietin-independent type 2 T-helper responses},

author = {Adrien Brulefert and Astrid Hoste and Quentin Muller and Jean-Daniel Fauny and Christopher G Mueller and Vincent Flacher},

doi = {10.1111/all.14718},

issn = {1398-9995},

year  = {2020},

date = {2020-01-01},

journal = {Allergy},

abstract = {BACKGROUND: Immune modulation by vitamin D3 through dendritic cells (DCs) remains controversial. Human DCs exposed in vitro counteract type-1 T-helper (Th1) differentiation and induce regulatory T cells. However, cutaneous application on mice promotes Th2-driven inflammation resembling atopic dermatitis and relying on thymic stromal lymphopoietin (TSLP) from keratinocytes and T-cell orientation by TSLP-stimulated skin DCs. We studied the effects of vitamin D3 in human skin, focusing on TSLP production and the role of skin DCs in T-cell differentiation. 

METHODS: Human healthy skin explants were exposed in vitro to vitamin D3 analogs. Migrating DCs were analyzed and TSLP quantified in the supernatant. Allogeneic naïve CD4+ T cells were cocultured with DCs to assess their proliferation and cytokine production. 

RESULTS: Vitamin D3 induced skin DCs to differentiate Th2 cells producing IL-4 and IL-13. Vitamin D3 triggered TSLP release in textasciitilde30% of skin explants, correlating with IL-13 detection in Th2 cells. In these donors, blocking TSLP receptor during skin explant cultures abrogated IL-13 production, yet IL-4+ Th2 cells were unaffected. Among skin DCs emerged CD14+ cells that had responded directly to vitamin D3 and differed from classical CD14+ dermal emigrants. Vitamin D3-elicited CD14+ DCs sufficed to promote IL-4+ Th2 cells in a TSLP-independent manner. 

CONCLUSION: Vitamin D3, despite inducing TSLP in some donors, had a direct influence on skin DCs, affecting their phenotype and ability to drive Th2 responses independently of TSLP. Our findings pave the way toward in vitro systems that accurately model human cutaneous Th2 responses, notably involved in atopic dermatitis.},

keywords = {atopic dermatitis, Dendritic cell, T helper 2, Team-Mueller, thymic stromal lymphopoietin, vitamin D3},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{mueller_skin_2019,

title = {Of skin and bone: did Langerhans cells and osteoclasts evolve from a common ancestor?},

author = {Christopher G Mueller and Benjamin Voisin},

doi = {10.1111/joa.12543},

issn = {1469-7580},

year  = {2019},

date = {2019-08-01},

journal = {Journal of Anatomy},

volume = {235},

number = {2},

pages = {412--417},

abstract = {Skin Langerhans cells are antigen-presenting cells of the interfollicular epidermis and the upper part of the hair follicle, whereas osteoclasts are specialized bone-resorbing macrophages. Although at first view these two cell types appear to have little in common, a closer analysis reveals shared features, and when taking into account their surrounding environment, a hypothesis can be developed that Langerhans cells and osteoclasts have evolved from a common ancestral cell type. In this mini-review, we have compared the ontogenetic features of Langerhans cells and osteoclasts from a genetic and a functional point of view, an issue that so far has been overlooked. The gene programs that control cell differentiation, and the body parts where they reside, present surprising similarities. Whereas the function of osteoclasts in bone degradation has been established since the first vertebrates, Langerhans cells may have undergone a stepwise adaptation from aquatic to terrestrial life. Their cell function co-evolved with the imperatives of the skin to protect against physical impact, heat, water loss and pathogens, which implied the capacity of Langerhans cells to associate with skin appendages and to develop immunostimulatory functions. For the highly versatile and efficient immune system of modern vertebrates, Langerhans cells may be a memory of the past.},

keywords = {Animals, Biological Evolution, Dendritic cell, Evolution, hair follicle, Humans, Langerhans cell, Langerhans Cells, Macrophage, OSTEOCLAST, Osteoclasts, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@article{navet_maternal_2018,

title = {Maternal RANKL Reduces the Osteopetrotic Phenotype of Null Mutant Mouse Pups},

author = {Benjamin Navet and Jorge William Vargas-Franco and Andrea Gama and Jérome Amiaud and Yongwon Choi and Hideo Yagita and Christopher G Mueller and Françoise Rédini and Dominique Heymann and Beatriz Castaneda and Frédéric Lézot},

doi = {10.3390/jcm7110426},

issn = {2077-0383},

year  = {2018},

date = {2018-11-01},

journal = {Journal of Clinical Medicine},

volume = {7},

number = {11},

abstract = {RANKL signalization is implicated in the morphogenesis of various organs, including the skeleton. Mice invalidated for Rankl present an osteopetrotic phenotype that was less severe than anticipated, depending on RANKL's implication in morphogenesis. The hypothesis of an attenuated phenotype, as a result of compensation during gestation by RANKL of maternal origin, was thus brought into question. In order to answer this question, Rankl null mutant pups from null mutant parents were generated, and the phenotype analyzed. The results validated the presence of a more severe osteopetrotic phenotype in the second-generation null mutant with perinatal lethality. The experiments also confirmed that RANKL signalization plays a part in the morphogenesis of skeletal elements through its involvement in cell-to-cell communication, such as in control of osteoclast differentiation. To conclude, we have demonstrated that the phenotype associated with Rankl invalidation is attenuated through compensation by RANKL of maternal origin.},

keywords = {bone, mandible, Morphogenesis, OSTEOCLAST, RANKL, skeletal growth, Team-Mueller, Tooth},

pubstate = {published},

tppubtype = {article}

}

@article{reynard_mannoside_2018,

title = {Mannoside Glycolipid Conjugates Display Antiviral Activity Against Ebola Virus},

author = {Olivier Reynard and Evelyne Schaeffer and Valentina A Volchkova and Andrea Cimarelli and Christopher G Mueller and Viktor E Volchkov},

doi = {10.1093/infdis/jiy464},

issn = {1537-6613},

year  = {2018},

date = {2018-11-01},

journal = {The Journal of Infectious Diseases},

volume = {218},

number = {suppl_5},

pages = {S666--S671},

abstract = {The West African outbreak of Ebola virus (EBOV) infection during 2013-2016 highlighted the need for development of field-applicable therapeutic drugs for this infection. Here we report that mannoside glycolipid conjugates (MGCs) consisting of a trimannose head and a lipophilic chain assembled by a linker inhibit EBOV infection not only of human monocyte-derived dendritic cells and macrophages, but also of a number of susceptible cells. Analysis of the mode of action leads us to conclude that MGCs act directly on cells, notably by preventing virus endocytosis.},

keywords = {Animals, Antiviral Agents, Chlorocebus aethiops, Ebolavirus, Glycolipids, Humans, Mannosides, Team-Mueller, Vero Cells, Virus Internalization},

pubstate = {published},

tppubtype = {article}

}

@article{navet_intrinsic_2018,

title = {The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases},

author = {Benjamin Navet and Kosei Ando and Jorge William Vargas-Franco and Régis Brion and Jérome Amiaud and Kanji Mori and Hideo Yagita and Christopher G Mueller and Franck Verrecchia and Clotilde Dumars and Marie-Françoise Heymann and Dominique Heymann and Frédéric Lézot},

doi = {10.3390/cancers10110398},

issn = {2072-6694},

year  = {2018},

date = {2018-10-01},

journal = {Cancers},

volume = {10},

number = {11},

abstract = {Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.},

keywords = {bone, metastases, osteosarcoma, RANKL/RANK, T-Lymphocyte, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{schaeffer_inhibition_2018,

title = {Inhibition of dengue virus infection by mannoside glycolipid conjugates},

author = {Evelyne Schaeffer and Vincent Flacher and Patrick Neuberg and Astrid Hoste and Adrien Brulefert and Jean-Daniel Fauny and Alain Wagner and Christopher G Mueller},

doi = {10.1016/j.antiviral.2018.04.005},

issn = {1872-9096},

year  = {2018},

date = {2018-01-01},

journal = {Antiviral Research},

volume = {154},

pages = {116--123},

abstract = {Dengue virus (DENV), a mosquito-borne flavivirus, causes severe and potentially fatal symptoms in millions of infected individuals each year. Although dengue fever represents a major global public health problem, the vaccines or antiviral drugs proposed so far have not shown sufficient efficacy and safety, calling for new antiviral developments. Here we have shown that a mannoside glycolipid conjugate (MGC) bearing a trimannose head with a saturated lipid chain inhibited DENV productive infection. It showed remarkable cell promiscuity, being active in human skin dendritic cells, hepatoma cell lines and Vero cells, and was active against all four DENV serotypes, with an IC50 in the low micromolar range. Time-of-addition experiments and structure-activity analyses revealed the importance of the lipid chain to interfere with an early viral infection step. This, together with a correlation between antiviral activity and membrane polarization by the lipid moiety indicated that the inhibitor functions by blocking viral envelope fusion with the endosome membrane. These finding establish MGCs as a novel class of antivirals against the DENV.},

keywords = {Cell Membrane, Dendritic Cells, Dengue virus, I2CT, Imagerie, inhibitors, Macrophages, Skin, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{schaeffer_inhibition_2018b,

title = {Inhibition of dengue virus infection by mannoside glycolipid conjugates},

author = {Evelyne Schaeffer and Vincent Flacher and Patrick Neuberg and Astrid Hoste and Adrien Brulefert and Jean-Daniel Fauny and Alain Wagner and Christopher G Mueller},

doi = {10.1016/j.antiviral.2018.04.005},

issn = {1872-9096},

year  = {2018},

date = {2018-01-01},

journal = {Antiviral Research},

volume = {154},

pages = {116--123},

abstract = {Dengue virus (DENV), a mosquito-borne flavivirus, causes severe and potentially fatal symptoms in millions of infected individuals each year. Although dengue fever represents a major global public health problem, the vaccines or antiviral drugs proposed so far have not shown sufficient efficacy and safety, calling for new antiviral developments. Here we have shown that a mannoside glycolipid conjugate (MGC) bearing a trimannose head with a saturated lipid chain inhibited DENV productive infection. It showed remarkable cell promiscuity, being active in human skin dendritic cells, hepatoma cell lines and Vero cells, and was active against all four DENV serotypes, with an IC50 in the low micromolar range. Time-of-addition experiments and structure-activity analyses revealed the importance of the lipid chain to interfere with an early viral infection step. This, together with a correlation between antiviral activity and membrane polarization by the lipid moiety indicated that the inhibitor functions by blocking viral envelope fusion with the endosome membrane. These finding establish MGCs as a novel class of antivirals against the DENV.},

keywords = {Animals, Antiviral Agents, Cell Line, Cell Membrane, Chemistry, Chlorocebus aethiops, Dendritic Cells, Dengue, Dengue virus, development, Drug, Drug Discovery, Flavivirus, function, Fusion, Glycolipids, Health, Hep G2 Cells, Human, Humans, immunopathology, infection, inhibition, inhibitors, Inhibitory Concentration 50, lipid, Macrophages, Mannosides, Membrane, Serogroup, Skin, Team-Mueller, vaccine, Vaccines, Vero Cells, viral Infection, virus, Virus Replication},

pubstate = {published},

tppubtype = {article}

}

@article{mueller_molecular_2018,

title = {Molecular and Cellular Requirements for the Assembly of Tertiary Lymphoid Structures},

author = {C G Mueller and S Nayar and J Campos and F Barone},

doi = {10.1007/978-3-319-78127-3_4},

issn = {0065-2598},

year  = {2018},

date = {2018-01-01},

journal = {Advances in Experimental Medicine and Biology},

volume = {1060},

pages = {55--72},

abstract = {At sites of chronic inflammation, recruited immune cells form structures that resemble secondary lymphoid organs (SLOs). Those are characterized by segregated areas of prevalent T- or B-cell aggregation, differentiation of high endothelial venules (HEVs) and local activation of resident stromal cells. B-cell proliferation and affinity maturation towards locally displayed autoantigens have been demonstrated at those sites, known as tertiary lymphoid structures (TLSs). TLS formation has been associated with local disease persistence and progression as well as increased systemic manifestations. While bearing a similar histological structure to SLO, the signals that regulate TLS and SLO formation can diverge, and a series of pro-inflammatory cytokines has been ascribed as responsible for TLS formation at different anatomical sites. Here we review the structural elements as well as the signals responsible for TLS aggregation, aiming to provide an overview to this complex immunological phenomenon.},

keywords = {Animals, CCL21, CXCL13, Endothelial and stromal cells, Humans, Lymphotoxin, Molecular Targeted Therapy, RANKL, Sjögren’s syndrome, Team-Mueller, Tertiary lymphoid structures, TNF},

pubstate = {published},

tppubtype = {article}

}