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  1. Article ; Online: Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases

    Philippe Georgel

    Cells, Vol 10, Iss 1134, p

    2021  Volume 1134

    Abstract: Interleukin-1β (IL-1β) and type I interferons (IFNs) are major cytokines involved in autoinflammatory/autoimmune diseases. Separately, the overproduction of each of these cytokines is well described and constitutes the hallmark of inflammasomopathies and ...

    Abstract Interleukin-1β (IL-1β) and type I interferons (IFNs) are major cytokines involved in autoinflammatory/autoimmune diseases. Separately, the overproduction of each of these cytokines is well described and constitutes the hallmark of inflammasomopathies and interferonopathies, respectively. While their interaction and the crosstalk between their downstream signaling pathways has been mostly investigated in the frame of infectious diseases, little information on their interconnection is still available in the context of autoinflammation promoted by sterile triggers. In this review, we will examine the respective roles of IL-1β and type I IFNs in autoinflammatory/rheumatic diseases and analyze their potential connections in the pathophysiology of some of these diseases, which could reveal novel therapeutic opportunities.
    Keywords inflammation ; type I interferons ; interleukin-1β ; crosstalk ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Pacific island nations face an urgent need for actions and future research on COVID-19

    Noellie Gay / Caroline van Gemert / Onofre Edwin Merilles, Jr / Philippe Georgel

    The Lancet Regional Health. Western Pacific, Vol 18, Iss , Pp 100326- (2022)

    2022  

    Keywords Public aspects of medicine ; RA1-1270
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Measuring the transcriptome-wide effects of aging on murine adipocytes using RNAseq

    Aurore De Cauwer / Angélique Pichot / Anne Molitor / Tristan Stemmelen / Raphael Carapito / Seiamak Bahram / Philippe Georgel

    STAR Protocols, Vol 4, Iss 3, Pp 102397- (2023)

    2023  

    Abstract: Summary: Adipose tissue plays a central role in age-related diseases. While RNAseq protocols exist for many tissues, few data have been generated with this technology to explore gene expression in adipocytes, particularly during aging. Here, we present a ...

    Abstract Summary: Adipose tissue plays a central role in age-related diseases. While RNAseq protocols exist for many tissues, few data have been generated with this technology to explore gene expression in adipocytes, particularly during aging. Here, we present a protocol to analyze the transcriptional changes that occur in adipose tissue during normal and accelerated aging in mouse models. We describe steps for genotyping, diet control, euthanasia, and dissection. We then detail RNA purification and genome-wide data generation and analysis.For complete details on the use and execution of this protocol, please refer to De Cauwer et al. (2022) iScience. Sep 16;25(10):105149. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords RNAseq ; Model Organisms ; Gene Expression ; Science (General) ; Q1-390
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates

    Eleonore Ostermann / Cécile Macquin / Wojciech Krezel / Seiamak Bahram / Philippe Georgel

    Viruses, Vol 7, Iss 5, Pp 2308-

    2015  Volume 2320

    Abstract: Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, ... ...

    Abstract Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis.
    Keywords Murine Cytomegalovirus ; Dicer ; encephalitis ; imaging ; Microbiology ; QR1-502 ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2015-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The Therapeutic Effect of Phosphopeptide P140 Attenuates Inflammation Induced by Uric Acid Crystals in Gout Arthritis Mouse Model

    Izabela Galvão / Dylan Mastrippolito / Laura Talamini / Mariana Aganetti / Victor Rocha / Cindy Verdot / Viviani Mendes / Vivian Louise Soares de Oliveira / Amanda Dias Braga / Vinicius Dantas Martins / Ana Maria Caetano de Faria / Flávio A. Amaral / Philippe Georgel / Angélica T. Vieira / Sylviane Muller

    Cells, Vol 11, Iss 3709, p

    2022  Volume 3709

    Abstract: Gout is a painful form of inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints. The aim of this study was to investigate the effect of peptide P140 on the inflammatory responses in crystal-induced mouse ... ...

    Abstract Gout is a painful form of inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints. The aim of this study was to investigate the effect of peptide P140 on the inflammatory responses in crystal-induced mouse models of gout and cell models including MSU-treated human cells. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. Injection of MSU crystals subcutaneously into the hind paw induced edema and increased pro-inflammatory cytokines levels. Treatment with P140 effectively reduced hypernociception, the neutrophil influx, and pro-inflammatory cytokine levels in these experimental models. Furthermore, P140 modulated neutrophils chemotaxis in vitro and increased apoptosis pathways through augmented caspase 3 activity and reduced NFκB phosphorylation. Moreover, P140 increased the production of the pro-resolving mediator annexin A1 and decreased the expression of the autophagy-related ATG5-ATG12 complex and HSPA8 chaperone protein. Overall, these findings suggest that P140 exerts a significant beneficial effect in a neutrophilic inflammation observed in the model of gout that can be of special interest in the design of new therapeutic strategies.
    Keywords MSU crystal-induced inflammation ; pain ; inflammasome ; neutrophil ; autophagy ; peptide therapy ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Identification of Mouse Cytomegalovirus Resistance Loci by ENU Mutagenesis

    Philippe Georgel / Karine Crozat

    Viruses, Vol 1, Iss 3, Pp 460-

    2009  Volume 483

    Abstract: Host resistance to infection depends on the efficiency with which innate immune responses keep the infectious agent in check. Innate immunity encompasses components with sensing, signaling and effector properties. These elements with nonredundant ... ...

    Abstract Host resistance to infection depends on the efficiency with which innate immune responses keep the infectious agent in check. Innate immunity encompasses components with sensing, signaling and effector properties. These elements with nonredundant functions are encoded by a set of host genes, the resistome. Here, we review our findings concerning the resistome. We have screened randomly mutagenized mice for susceptibility to a natural opportunistic pathogen, the mouse cytomegalovirus. We found that some genes with initially no obvious functions in innate immunity may be critical for host survival to infections, falling into a newly defined category of genes of the resistome.
    Keywords N-ethyl-N-nitrosourea ; mutagenesis ; resistome ; mouse cytomegalovirus ; susceptibility ; innate immunity ; homeostasis ; Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2009-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Contrasting role of NLRP12 in autoinflammation

    Alain Meyer / François Maurier / Angélique Pichot / Philippe Georgel / Raphael Carapito / Anne Molitor / Dan Lévy / Alexandre Mariotte / Aurore DeCauwer / Cecile Macquin

    RMD Open, Vol 7, Iss

    evidence from a case report and mouse models

    2021  Volume 3

    Keywords Medicine ; R
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes.

    Philippe Georgel / Cécile Macquin / Seiamak Bahram

    PLoS ONE, Vol 4, Iss 11, p e

    2009  Volume 7803

    Abstract: Toll-Like Receptors (TLR) are critical elements of the innate arm of the vertebrate immune system. They constitute a multigenic family of receptors which collectively bind a diverse array of--exogeneous as well as endogeneous--ligands. An exponential ... ...

    Abstract Toll-Like Receptors (TLR) are critical elements of the innate arm of the vertebrate immune system. They constitute a multigenic family of receptors which collectively bind a diverse array of--exogeneous as well as endogeneous--ligands. An exponential burst of knowledge has defined their biological role in fight against infections and generation/modulation of auto-immune disorders. Hence, they could at least be conceptually recognized--despite being structurally unrelated - as innate counterparts to Major Histocompatibility Complex (MHC) molecules--equally recognizing antigenic ligands (albeit structurally more homogeneous i.e., peptides), again derived from self and/or non-self sources--preeminent this time in adaptive immunity. Our great disparities in face of infections and/or susceptibility to auto-immune diseases have provoked an intense search for genetic explanations, in part satisfied by the extraordinary MHC allelic repertoire. An equally in-depth and systematic analysis of TLR diversity is lacking despite numerous independent reports of a growing number of SNPs within these loci. The work described here aims at providing a preliminary picture of the allelic repertoire--and not purely SNPs--of all 10 human TLR coding sequences (with exception of TLR3) within a single cohort of up to 100 individuals. It appears from our work that TLR are unequally polymorphic: TLR2 (DNA alleles: 7/protein alleles: 3), 4 (4/3), 7 (6/3), 8 (9/2) and 9 (8/3) being comparatively least diverse whereas TLR1 (11/10), 5 (14/12), 6 (10/8) and 10 (15/10) show a substantial number of alleles. In addition to allelic assignment of a large number of SNPs, 10 new polymorphic positions were hereby identified. Hence this work depicts a first overview of the diversity of almost all human TLR genes, a prelude for large-scale population genetics as well as genetic association studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2009-11-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides.

    Pilar Domingo-Calap / Benjamin Schubert / Mélanie Joly / Morgane Solis / Meiggie Untrau / Raphael Carapito / Philippe Georgel / Sophie Caillard / Samira Fafi-Kremer / Nicodème Paul / Oliver Kohlbacher / Fernando González-Candelas / Seiamak Bahram

    PLoS Pathogens, Vol 14, Iss 10, p e

    2018  Volume 1007368

    Abstract: Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our ... ...

    Abstract Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(-3)-10(-5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo

    Cédric Schleiss / Wassila Ilias / Ouria Tahar / Yonca Güler / Laurent Miguet / Caroline Mayeur-Rousse / Laurent Mauvieux / Luc-Matthieu Fornecker / Elise Toussaint / Raoul Herbrecht / Frédéric Bertrand / Myriam Maumy-Bertrand / Thierry Martin / Sylvie Fournel / Philippe Georgel / Seiamak Bahram / Laurent Vallat

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Abstract A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo ...

    Abstract Abstract A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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