4 results on '"Heike Hildebrandt"'
Number of results to display per page
Search Results
2. Human pDCs display sex-specific differences in type I interferon subtypes and interferon α/β receptor expression
- Author
-
Heike Hildebrandt, Morgane Griesbeck, Claudia Beisel, Susanne Ziegler, Kathrin Sutter, Marcus Altfeld, Sven Hendrik Hagen, and Ulf Dittmer
- Subjects
Adult ,Male ,0301 basic medicine ,Receptor expression ,Immunology ,Medizin ,Stimulation ,Receptor, Interferon alpha-beta ,Biology ,Pathogenesis ,03 medical and health sciences ,Interferon ,medicine ,Humans ,Immunology and Allergy ,RNA, Messenger ,Receptor ,Cells, Cultured ,Sex Characteristics ,hemic and immune systems ,Dendritic Cells ,TLR7 ,030104 developmental biology ,Toll-Like Receptor 7 ,Interferon Type I ,Female ,Immunization ,Sex ,Signal transduction ,Transcriptome ,Interferon type I ,Signal Transduction ,medicine.drug - Abstract
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN-α subtypes. In addition, pDCs from females had higher levels of IFN-β mRNA after stimulation, indicating that sex differences in IFN-I production by pDCs were mediated by a signaling event upstream of the first loop of IFN-I mRNA transcription. Furthermore, the surface expression levels of the common IFN-α/β receptor subunit 2 were significantly higher on pDCs from females in comparison to males. These data indicate that higher IFN-α production is already established at the mRNA level and propose a contribution of higher IFN-α/β receptor 2 expression on pDCs to the immunological differences in IFN-I production observed between females and males.
- Published
- 2017
- Full Text
- View/download PDF
3. Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women
- Author
-
Heike Hildebrandt, Jean-Philippe Herbeuval, Susanne Ziegler, Claudia Beisel, Marcus Altfeld, Sophie Laffont, Michael Sirignano, Brigitte Autran, Nikaïa Smith, Jean-Charles Guéry, Armon Sharei, Sylvie Le Gall, Lise Chauveau, Meghan G. Hart, Olivier Schwartz, Thomas J. Diefenbach, Phillip Tomezsko, Georgio Kourjian, Filippos Porichis, Christine D. Palmer, Morgane Griesbeck, J. Judy Chang, Alexandra-Chloé Villani, Claire Cenac, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ragon Institute of MGH, MIT and Harvard, Heinrich-Pette-Institut, Leibniz Institute for Experimental Virology, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Medical Department [Hamburg], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Infectious Diseases [Monash], Monash University [Melbourne], This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grants R01 AI078784 and P01 AI078897, fellowships from the National Health and Medical Research Council of Australia (Grant 519578 to J.J.C.), a Ragon Fellowship from The Phillip T. and Susan M. Ragon Foundation (to J.J.C.), a fellowship from the French National Agency for Research on AIDS and Viral Hepatitis (Grant 2013-219 to M.G.), the Fondation pour la Recherche Médicale (Grant DEQ2000329169 to J.-C.G.), the Conseil Régional Midi-Pyrénées (J.-C.G.), the Arthritis Fondation Courtin (J.-C.G.), and the Fondation ARC pour la recherche sur le cancer (J.-C.G.), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Massachusetts Institute of Technology ( MIT ), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston] ( MGH ) -Massachusetts Institute of Technology ( MIT ), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Koch Institute for Integrative Cancer Research at MIT [Cambridge, MA], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Innate Immunity and Inflammation ,Immunology ,Estrogen receptor ,Mice, Transgenic ,Plasmacytoid dendritic cell ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Animals ,Humans ,Immunology and Allergy ,RNA, Messenger ,Cells, Cultured ,030304 developmental biology ,Regulation of gene expression ,Sex Characteristics ,0303 health sciences ,[ SDV ] Life Sciences [q-bio] ,Estrogen Receptor alpha ,Interferon-alpha ,hemic and immune systems ,Dendritic Cells ,TLR7 ,Recombinant Proteins ,Endocrinology ,Gene Expression Regulation ,Toll-Like Receptor 7 ,Interferon Regulatory Factors ,Female ,Estrogen receptor alpha ,IRF5 ,Signal Transduction ,030215 immunology ,Interferon regulatory factors - Abstract
Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α–secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.
- Published
- 2015
- Full Text
- View/download PDF
4. ID: 141
- Author
-
Heike Hildebrandt, Marcus Altfeld, Susanne Ziegler, Claudia Beisel, Kathrin Gibbert, and Morgane Griesbeck
- Subjects
Immunology ,Stimulation ,Viremia ,Hematology ,TLR7 ,Biology ,medicine.disease ,Type I interferon production ,Biochemistry ,Peripheral blood mononuclear cell ,Pathogenesis ,Viral replication ,medicine ,Immunology and Allergy ,Molecular Biology ,Gene - Abstract
The outcomes of many diseases differ between women and men, with women having a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases, including influenza and HIV-1. In HIV-1 infection, clinical studies have shown faster disease progression and stronger immune activation in females compared to males for the same level of viral replication, as well as better control of initial viremia in women during primary infection (Meier, 2009; Sterling, 2001; Farzadegan, 1998). It has been suggested that this is partially due to TLR-mediated activation of pDC, the main producers of IFN- α , in response to HIV-1 ssRNA. We investigated the induction of type I interferons upon TLR7/8 stimulation on sorted pDC. PBMCs were stimulated for 2 h with a synthetic TLR7/8 ligand. pDC cells were isolated by flow-based sorting and subsequently mRNA was isolated. qRT-PCR revealed a sex-specific differential expression of type I Interferons, with pDC from females showing a higher expression level of corresponding interferons compared to males, including all IFN α -subtypes (p = 0.003), as well as type III Interferons (IFN λ 1 p = 0.03). Of note, pDCs from females also showed higher IFN β expression (p = 0.059), which is part of the initial wave of gene transcription that triggers a positive feedback loop, leading to the induction of additional IFN α -encoding genes. These data demonstrate that sex-specific differences described in response to HIV-1 are associated with enhanced expression of several Interferons, with IFN β being potentially responsible for the initiation of differential type I Interferon production between males and females.
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.