Pathogenesis of bacterial infections and immunity

@article{arquier_brain_2021,

title = {Brain adiponectin signaling controls peripheral insulin response in Drosophila},

author = {Nathalie Arquier and Marianne Bjordal and Philippe Hammann and Lauriane Kuhn and Pierre Léopold},

doi = {10.1038/s41467-021-25940-6},

issn = {2041-1723},

year  = {2021},

date = {2021-09-01},

journal = {Nature Communications},

volume = {12},

number = {1},

pages = {5633},

abstract = {The brain plays a key role in energy homeostasis, detecting nutrients, metabolites and circulating hormones from peripheral organs and integrating this information to control food intake and energy expenditure. Here, we show that a group of neurons in the Drosophila larval brain expresses the adiponectin receptor (AdipoR) and controls systemic growth and metabolism through insulin signaling. We identify glucose-regulated protein 78 (Grp78) as a circulating antagonist of AdipoR function produced by fat cells in response to dietary sugar. We further show that central AdipoR signaling inhibits peripheral Juvenile Hormone (JH) response, promoting insulin signaling. In conclusion, we identify a neuroendocrine axis whereby AdipoR-positive neurons control systemic insulin response.},

keywords = {Adiponectin, Animals, Brain, Cell Line, Drosophila melanogaster, Drosophila Proteins, Energy Metabolism, Genetically Modified, Hemolymph, Homeostasis, Insulin, Juvenile Hormones, Larva, Neurons, PPSE, Receptors, Signal Transduction},

pubstate = {published},

tppubtype = {article}

}

@article{dahlet_e2f6_2021,

title = {E2F6 initiates stable epigenetic silencing of germline genes during embryonic development},

author = {Thomas Dahlet and Matthias Truss and Ute Frede and Hala Al Adhami and Anaïs F. Bardet and Michael Dumas and Judith Vallet and Johana Chicher and Philippe Hammann and Sarah Kottnik and Peter Hansen and Uschi Luz and Gonzalo Alvarez and Ghislain Auclair and Jochen Hecht and Peter N. Robinson and Christian Hagemeier and Michael Weber},

doi = {10.1038/s41467-021-23596-w},

issn = {2041-1723},

year  = {2021},

date = {2021-06-01},

journal = {Nature Communications},

volume = {12},

number = {1},

pages = {3582},

abstract = {In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.},

keywords = {Animals, Binding Sites, Cell Differentiation, CpG Islands, CRISPR-Cas Systems, DNA Methylation, E2F6 Transcription Factor, Embryonic Development, Epigenesis, Gene Silencing, Genetic, Germ Cells, Knockout, Mice, Mouse Embryonic Stem Cells, Polycomb Repressive Complex 1, PPSE, RNA, Small Interfering},

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{bordoni_stimulation_2019,

title = {Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo},

author = {Valentina Bordoni and Giacomo Reina and Marco Orecchioni and Giulia Furesi and Stefanie Thiele and Chiara Gardin and Barbara Zavan and Gianaurelio Cuniberti and Alberto Bianco and Martina Rauner and Lucia G Delogu},

doi = {10.1039/c9nr03975a},

issn = {2040-3372},

year  = {2019},

date = {2019-11-01},

journal = {Nanoscale},

volume = {11},

number = {41},

pages = {19408--19421},

abstract = {Nanosystems are able to enhance bone regeneration, a complex process requiring the mutual interplay between immune and skeletal cells. Activated monocytes can communicate pro-osteogenic signals to mesenchymal stem cells and promote osteogenesis. Thus, the activation of monocytes is a promising strategy to improve bone regeneration. Nanomaterials specifically selected to provoke immune-mediated bone formation are still missing. As a proof of concept, we apply here the intrinsic immune-characteristics of graphene oxide (GO) with the well-recognized osteoinductive capacity of calcium phosphate (CaP) in a biocompatible nanomaterial called maGO-CaP (monocytes activator GO complexed with CaP). In the presence of monocytes, the alkaline phosphatase activity and the expression of osteogenic markers increased. Studying the mechanisms of action, we detected an up-regulation of Wnt and BMP signaling, two key osteogenic pathways. The role of the immune activation was evidenced by the over-production of oncostatin M, a pro-osteogenic factor produced by monocytes. Finally, we tested the pro-osteogenic effects of maGO-CaP in vivo. maGO-CaP injected into the tibia of mice enhanced local bone mass and the bone formation rate. Our study suggests that maGO-CaP can activate monocytes to enhance osteogenesis ex vivo and in vivo.},

keywords = {Animals, Biocompatible Materials, Bone Morphogenetic Protein 2, Calcium Phosphates, Cell Differentiation, Cell Survival, Coculture Techniques, Graphite, Humans, I2CT, Inbred C57BL, Male, Mesenchymal Stem Cells, Mice, Monocytes, Oncostatin M, Osteoblasts, Osteogenesis, Signal Transduction, Team-Bianco, Tibia, Wnt Proteins},

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{fillatre_teads_2019,

title = {TEADs, Yap, Taz, Vgll4s transcription factors control the establishment of Left-Right asymmetry in zebrafish},

author = {Jonathan Fillatre and Jean-Daniel Fauny and Jasmine Alexandra Fels and Cheng Li and Mary Goll and Christine Thisse and Bernard Thisse},

doi = {10.7554/eLife.45241},

issn = {2050-084X},

year  = {2019},

date = {2019-01-01},

journal = {eLife},

volume = {8},

abstract = {In many vertebrates, establishment of Left-Right (LR) asymmetry results from the activity of a ciliated organ functioning as the LR Organizer (LRO). While regulation of the formation of this structure by major signaling pathways has been described, the transcriptional control of LRO formation is poorly understood. Using the zebrafish model, we show that the transcription factors and cofactors mediating or regulating the transcriptional outcome of the Hippo signaling pathway play a pivotal role in controlling the expression of genes essential to the formation of the LRO including ligands and receptors of signaling pathways involved in this process and most genes required for motile ciliogenesis. Moreover, the transcription cofactor, Vgll4l regulates epigenetic programming in LRO progenitors by controlling the expression of writers and readers of DNA methylation marks. Altogether, our study uncovers a novel and essential role for the transcriptional effectors and regulators of the Hippo pathway in establishing LR asymmetry.},

keywords = {Animals, Body Patterning, Developmental, developmental biology, Gene Expression Regulation, Hippo pathway, I2CT, Imagerie, Left-Right asymmetry, Left-Right Organizer, Signal Transduction, Taz, Transcription Factors, Vgll4, Yap, Zebrafish},

pubstate = {published},

tppubtype = {article}

}

@article{murera_few_2019,

title = {Few layer graphene does not affect the function and the autophagic activity of primary lymphocytes},

author = {Diane Murera and Sowmya Malaganahalli and Cristina Martín and Giacomo Reina and Jean-Daniel Fauny and Hélène Dumortier and Ester Vázquez and Alberto Bianco},

doi = {10.1039/c9nr00846b},

issn = {2040-3372},

year  = {2019},

date = {2019-01-01},

journal = {Nanoscale},

volume = {11},

number = {21},

pages = {10493--10503},

abstract = {Carbon-based nanomaterials represent a new tool in future medical applications. Thus, focusing on the evaluation of the degree of their safety has been growing in the last years. In this study we were particularly interested in understanding the impact of few layer graphene (FLG) on primary murine lymphocytes. These B and T cells, that are the second, but specialized, line of defense of the immune system, rely on various mechanisms to ensure their efficient function and maintenance. One of these mechanisms is autophagy that can be triggered by various nanomaterials in some types of cells. For these reasons, we were interested in evaluating the way FLG could affect this process in lymphocytes. Our results point out that FLG neither impacts the viability and activation of T and B cells nor their autophagic activity. Using confocal microscopy, we were also able to see that FLG does not appear to cause any membrane damage and does not penetrate inside of these cells. Overall, our data do not show any effect of this material on lymphocyte homeostasis, which is one more argument in favor of the continuation of studies investigating the potential of FLG for therapeutic applications.},

keywords = {Animals, Autophagy, B-Lymphocytes, Dumortier, Graphite, I2CT, Inbred BALB C, Mice, Nanostructures, T-Lymphocytes, Team-Bianco, Team-Dumortier},

pubstate = {published},

tppubtype = {article}

}

@article{rauti_graphene_2019,

title = {Graphene Oxide Flakes Tune Excitatory Neurotransmission in Vivo by Targeting Hippocampal Synapses},

author = {Rossana Rauti and Manuela Medelin and Leon Newman and Sandra Vranic and Giacomo Reina and Alberto Bianco and Maurizio Prato and Kostas Kostarelos and Laura Ballerini},

doi = {10.1021/acs.nanolett.8b04903},

issn = {1530-6992},

year  = {2019},

date = {2019-01-01},

journal = {Nano Letters},

volume = {19},

number = {5},

pages = {2858--2870},

abstract = {Synapses compute and transmit information to connect neural circuits and are at the basis of brain operations. Alterations in their function contribute to a vast range of neuropsychiatric and neurodegenerative disorders and synapse-based therapeutic intervention, such as selective inhibition of synaptic transmission, may significantly help against serious pathologies. Graphene is a two-dimensional nanomaterial largely exploited in multiple domains of science and technology, including biomedical applications. In hippocampal neurons in culture, small graphene oxide nanosheets (s-GO) selectively depress glutamatergic activity without altering cell viability. Glutamate is the main excitatory neurotransmitter in the central nervous system and growing evidence suggests its involvement in neuropsychiatric disorders. Here we demonstrate that s-GO directly targets the release of presynaptic vesicle. We propose that s-GO flakes reduce the availability of transmitter, via promoting its fast release and subsequent depletion, leading to a decline ofglutamatergic neurotransmission. We injected s-GO in the hippocampus in vivo, and 48 h after surgery ex vivo patch-clamp recordings from brain slices show a significant reduction in glutamatergic synaptic activity in respect to saline injections.},

keywords = {Animals, Excitatory Amino Acid Agents, glutamate, Glutamic Acid, graphene, Graphite, hippocampal network, Hippocampus, Humans, I2CT, Nanostructures, Neurodegenerative Diseases, Neurons, Newborn, Primary Cell Culture, quantum dots, Rats, synapses, Synaptic Transmission, Team-Bianco, Wistar},

pubstate = {published},

tppubtype = {article}

}

@article{ji_physically-triggered_2019,

title = {Physically-triggered nanosystems based on two-dimensional materials for cancer theranostics},

author = {Ding-Kun Ji and Cécilia Ménard-Moyon and Alberto Bianco},

doi = {10.1016/j.addr.2018.08.010},

issn = {1872-8294},

year  = {2019},

date = {2019-01-01},

journal = {Advanced Drug Delivery Reviews},

volume = {138},

pages = {211--232},

abstract = {There is an increasing demand to develop effective methods for treating malignant diseases to improve healthcare in our society. Stimuli-responsive nanosystems, which can respond to internal or external stimuli are promising in cancer therapy and diagnosis due to their functionality and versatility. As a newly emerging class of nanomaterials, two-dimensional (2D) nanomaterials have attracted huge interest in many different fields including biomedicine due to their unique physical and chemical properties. In the past decade, stimuli-responsive nanosystems based on 2D nanomaterials have been widely studied, showing promising applications in cancer therapy and diagnosis, including phototherapies, magnetic therapy, drug and gene delivery, and non-invasive imaging. Here, we will focus our attention on the state-of-the-art of physically-triggered nanosystems based on graphene and two-dimensional nanomaterials for cancer therapy and diagnosis. The physical triggers include light, temperature, magnetic and electric fields.},

keywords = {2D Materials, Animals, Diagnosis, graphene, Graphite, Humans, I2CT, Light, Magnetic Fields, Nanomaterials, Nanostructures, Neoplasms, Team-Bianco, Theragnosis, Theranostic Nanomedicine, therapy},

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{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{ferreira_small_2018,

title = {The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis},

author = {Flávia Viana Ferreira and Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Karla Pollyanna Vieira de Oliveira and Emanuele Guimarães Silva and Maurício Roberto Viana Sant'Anna and Nelder Figueiredo de Gontijo and Erna Geessien Kroon and Jean-Luc Imler and João Trindade Marques},

doi = {10.1371/journal.pntd.0006569},

issn = {1935-2735},

year  = {2018},

date = {2018-01-01},

journal = {PLoS Negl Trop Dis},

volume = {12},

number = {6},

pages = {e0006569},

abstract = {Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.},

keywords = {Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral},

pubstate = {published},

tppubtype = {article}

}

@article{fadeel_safety_2018,

title = {Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment},

author = {Bengt Fadeel and Cyrill Bussy and Sonia Merino and Ester Vázquez and Emmanuel Flahaut and Florence Mouchet and Lauris Evariste and Laury Gauthier and Antti J Koivisto and Ulla Vogel and Cristina Martín and Lucia G Delogu and Tina Buerki-Thurnherr and Peter Wick and Didier Beloin-Saint-Pierre and Roland Hischier and Marco Pelin and Fabio Candotto Carniel and Mauro Tretiach and Fabrizia Cesca and Fabio Benfenati and Denis Scaini and Laura Ballerini and Kostas Kostarelos and Maurizio Prato and Alberto Bianco},

doi = {10.1021/acsnano.8b04758},

issn = {1936-086X},

year  = {2018},

date = {2018-01-01},

journal = {ACS nano},

volume = {12},

number = {11},

pages = {10582--10620},

abstract = {Graphene and its derivatives are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biological effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.},

keywords = {Animals, carbon nanomaterials, environment, Environmental Monitoring, Exposure, graphene, Graphite, hazard, Health, Humans, I2CT, life cycle assessment, Materials Testing, Nanostructures, Risk Assessment, safety, Structure-Activity Relationship, Team-Bianco, Toxicity},

pubstate = {published},

tppubtype = {article}

}

@article{rodrigues_immunological_2018,

title = {Immunological impact of graphene oxide sheets in the abdominal cavity is governed by surface reactivity},

author = {Artur Filipe Rodrigues and Leon Newman and Dhifaf A Jasim and Isabella A Vacchi and Cécilia Ménard-Moyon and Livia E Crica and Alberto Bianco and Kostas Kostarelos and Cyrill Bussy},

doi = {10.1007/s00204-018-2303-z},

issn = {1432-0738},

year  = {2018},

date = {2018-01-01},

journal = {Archives of Toxicology},

volume = {92},

number = {11},

pages = {3359--3379},

abstract = {Graphene oxide (GO) is an oxidised form of graphene that has attracted commercial interest in multiple applications, including inks, printed electronics and spray coatings, which all raise health concerns due to potential creation of inhalable aerosols. Although a number of studies have discussed the toxicity of GO sheets, the in vivo impact of their lateral dimensions is still not clear. Here, we compared the effects of large GO sheets (l-GO, 1-20 µm) with those of small GO sheets (s-GO, textbackslashtextless 1 µm) in terms of mesothelial damage and peritoneal inflammation, after intraperitoneal (i.p.) injection in mice. To benchmark the outcomes, long and rigid multi-walled carbon nanotubes (MWCNTs) that were shown to be associated with asbestos-like pathogenicity on the mesothelium were also tested. Our aim was to assess whether lateral dimensions can be a predictor of inflammogenicity for GO sheets in a similar fashion as length is for MWCNTs. While long MWCNTs dispersed in 0.5% BSA induced a granulomatous response on the diaphragmatic mesothelium and immune cell recruitment to the peritoneal cavity, GO sheets dispersed under similar conditions did not cause any response, regardless of their lateral dimensions. We further interrogated whether tuning the surface reactivity of GO by testing different dispersions (5% dextrose instead of 0.5% BSA) may change the biological outcome. Although the change of dispersion did not alter the impact of GO on the mesothelium (i.e. no granuloma), we observed that, when dispersed in protein-free 5% dextrose solution, s-GO elicited a greater recruitment of monocytic cells to the peritoneal cavity than l-GO, or when dispersed in protein-containing solution. Such recruitment coincided with the greater ability of s-GO to interact in vivo with peritoneal macrophages and was associated with a greater surface reactivity in comparison to l-GO. In conclusion, large dimension was not a determining factor of the immunological impact of GO sheets after i.p. administration. For an equal dose, GO sheets with lateral dimensions similar to the length of long MWCNTs were less pathogenic than the MWCNTs. On the other hand, surface reactivity and the ability of some smaller GO sheets to interact more readily with immune cells seem to be key parameters that can be tuned to improve the safety profile of GO. In particular, the choice of dispersion modality, which affected these two parameters, was found to be of crucial importance in the assessment of GO impact in this model. Overall, these findings are essential for a better understanding of the parameters governing GO toxicity and inflammation, and the rational design of safe GO-based formulations for various applications, including biomedicine.},

keywords = {2D Materials, Animals, carbon, Epithelium, Female, graphene oxide, Graphite, I2CT, In vivo, Inbred C57BL, inflammation, Intraperitoneal, Macrophages, Mesothelium, Mice, Nanotubes, Peritoneal, Peritoneal Cavity, Protein coating, Team-Bianco, Tissue Distribution, Toxicity},

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}

}

@article{mueller_cellular_2018,

title = {Cellular and Vascular Components of Tertiary Lymphoid Structures},

author = {Christopher George Mueller and Saba Nayar and David Gardner and Francesca Barone},

doi = {10.1007/978-1-4939-8709-2_2},

issn = {1940-6029},

year  = {2018},

date = {2018-01-01},

journal = {Methods in Molecular Biology (Clifton, N.J.)},

volume = {1845},

pages = {17--30},

abstract = {Inflammatory immune cells recruited at the site of chronic inflammation form structures that resemble secondary lymphoid organs (SLO). These are characterized by segregated areas of prevalent T- or B-cell aggregation, differentiation of high endothelial venules, and local activation of resident stromal cells, including lymphatic endothelial cells. B-cell proliferation and affinity maturation toward locally displayed autoantigens have been demonstrated at these sites, known as tertiary lymphoid structures (TLS). TLS formation during chronic inflammation 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 have been ascribed as responsible for TLS formation at different anatomical sites. Moreover, for a long time the structural compartment that regulates TLS homeostasis, including survival and recirculation of leucocytes has been neglected. In this chapter, we summarize the novel data available on TLS formation, structural organization, and the functional and anatomical links connecting TLS and SLOs.},

keywords = {Animals, Biomarkers, CCL21, Cell Survival, Cellular Microenvironment, CXCL13, Cytokines, Humans, Immunity, inflammation, Innate, LYMPHATIC VESSEL, Lymphocyte, Lymphocyte Subsets, Lymphotoxin, Multigene Family, Neovascularization, Pathologic, Receptors, Signal Transduction, Sjögren’s syndrome, Stromal cell, Team-Mueller, Tertiary lymphoid organ, Tertiary lymphoid structures, TNF-α, Tumor Necrosis Factor},

pubstate = {published},

tppubtype = {article}

}

@article{chypre_porphyrin_2017,

title = {Porphyrin Derivatives Inhibit the Interaction between Receptor Activator of NF-κB and Its Ligand},

author = {Mélanie Chypre and Maria-Bernadette Madel and Olivier Chaloin and Claudine Blin-Wakkach and Christophe Morice and Christopher G Mueller},

doi = {10.1002/cmdc.201700462},

issn = {1860-7187},

year  = {2017},

date = {2017-10-01},

journal = {ChemMedChem},

volume = {12},

number = {20},

pages = {1697--1702},

abstract = {Receptor activator of NF-κB (RANK), a member of the TNF-receptor superfamily, plays an important role in bone resorption and stimulates immune and epithelial cell activation. Denosumab, a human monoclonal antibody that blocks the RANK ligand (RANKL), is approved for the treatment of osteoporosis and bone metastasis. However, a small molecule that inhibits the RANK-RANKL interaction would be beneficial to decrease cost and to facilitate treatments with orally available therapeutic agents. Herein we report the discovery of the first nonpeptidic inhibitors of RANK-RANKL interactions. In screening a chemical library by competitive ELISA, the porphyrin verteporfin was identified as a hit. Derivatives were screened, and the chlorin-macrocycle-containing pheophorbide A and purpurin 18 were found to bind recombinant RANKL, to inhibit RANK-RANKL interactions in the ELISA, and to suppress the RANKL-dependent activation of model cells and the differentiation of RANK-expressing precursors into osteoclasts. This discovery of a family of small molecules that inhibit RANK activation presents an initial basis for further development of nonpeptidic therapeutic agents targeting the interaction between RANK and RANKL.},

keywords = {Animals, Cell Survival, cell-based assays, ELISA, Humans, Jurkat Cells, Mice, Molecular Structure, Osteoclasts, Osteogenesis, porphyrins, Protein Binding, RANK ligand, receptor activator of NF-κB, Receptor Activator of Nuclear Factor-kappa B, Structure-Activity Relationship, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{onder_lymphatic_2017,

title = {Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis},

author = {Lucas Onder and Urs Mörbe and Natalia Pikor and Mario Novkovic and Hung-Wei Cheng and Thomas Hehlgans and Klaus Pfeffer and Burkhard Becher and Ari Waisman and Thomas Rülicke and Jennifer Gommerman and Christopher G Mueller and Shinichiro Sawa and Elke Scandella and Burkhard Ludewig},

doi = {10.1016/j.immuni.2017.05.008},

issn = {1097-4180},

year  = {2017},

date = {2017-07-01},

journal = {Immunity},

volume = {47},

number = {1},

pages = {80--92.e4},

abstract = {Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event. LEC activation was mediated mainly by signaling through receptor activator of NF-κB (RANK) and the non-canonical NF-κB pathway and was steered by sphingosine-1-phosphate-receptor-dependent retention of LTi cells in the LN anlage. Finally, the finding that pharmacologically enforced interaction between LTi cells and LECs promotes ectopic LN formation underscores the central LTo function of LECs.},

keywords = {Animals, Cell Differentiation, Cells, Choristoma, Cultured, Embryo, Endothelial Cells, fibroblastic reticular cells, Inbred C57BL, lymph node organogenesis, Lymph Nodes, lymphatic and blood endothelial cells, lymphoid stromal cells, lymphoid tissue organizer cells, Lymphotoxin beta Receptor, Lysosphingolipid, Mammalian, Mesenchymal Stem Cells, mesenchymal stromal cells, Mice, NF-kappa B, Organogenesis, Receptor Activator of Nuclear Factor-kappa B, Receptors, Signal Transduction, Team-Mueller, transgenic},

pubstate = {published},

tppubtype = {article}

}

@article{gies_identification_2017b,

title = {Identification of autoreactive B cells with labeled nucleosomes},

author = {Vincent Gies and Alain Wagner and Cécile Seifert and Aurélien Guffroy and Jean-D. Fauny and Anne-M. Knapp and Jean-L. Pasquali and Thierry Martin and Hélène Dumortier and Anne-S. Korganow and Pauline Soulas-Sprauel},

doi = {10.1038/s41598-017-00664-0},

issn = {2045-2322},

year  = {2017},

date = {2017-01-01},

journal = {Scientific Reports},

volume = {7},

number = {1},

pages = {602},

abstract = {The pathogenesis of autoimmune diseases has not been completely elucidated yet, and only a few specific treatments have been developed so far. In autoimmune diseases mediated by pathogenic autoantibodies, such as systemic lupus erythematosus, the specific detection and analysis of autoreactive B cells is crucial for a better understanding of the physiopathology. Biological characterization of these cells may help to define new therapeutic targets. Very few techniques allowing the precise detection of autoreactive B cells have been described so far. Herein we propose a new flow cytometry technique for specific detection of anti-nucleosome B cells, which secrete autoantibodies in systemic lupus erythematosus, using labeled nucleosomes. We produced different fluorochrome-labeled nucleosomes, characterized them, and finally tested them in flow cytometry. Nucleosomes labeled via the cysteines present in H3 histone specifically bind to autoreactive B cells in the anti-DNA transgenic B6.56R mice model. The present work validates the use of fluorochrome-labeled nucleosomes via cysteines to identify anti-nucleosome B cells and offers new opportunities for the description of autoreactive B cell phenotype.},

keywords = {Animals, Autoantibodies, Autoantigens, Autoimmunity, B-Lymphocytes, Biomarkers, Cell Line, Dumortier, Female, Flow Cytometry, Humans, I2CT, Lupus Erythematosus, Mice, Nucleosomes, Staining and Labeling, Systemic, Team-Dumortier},

pubstate = {published},

tppubtype = {article}

}