title: An innate antiviral pathway acting before interferons at epithelial surfaces.
abstract: Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Marie B
authors.initials: MB
authors.lastname: Iversen
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Line S
authors.initials: LS
authors.lastname: Reinert
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Thomsen
authors.affiliation: Department of Cellular and Molecular Medicine, Centre for Glycomics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ieva
authors.initials: I
authors.lastname: Bagdonaite
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Ramya
authors.initials: R
authors.lastname: Nandakumar
authors.affiliation: Department of Pediatrics and Microbiology, Albert Einstein College of Medicine, New York, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Cheshenko
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Thaneas
authors.initials: T
authors.lastname: Prabakaran
authors.affiliation: Department of Cellular and Molecular Medicine, Centre for Glycomics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sergey Y
authors.initials: SY
authors.lastname: Vakhrushev
authors.affiliation: Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Malgosha
authors.initials: M
authors.lastname: Krzyzowska
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Sine K
authors.initials: SK
authors.lastname: Kratholm
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ruiz-Perez
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Steen V
authors.initials: SV
authors.lastname: Petersen
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
authors.affiliation: Department of Biostatistics, University of Aarhus, Aarhus, Denmark.
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Eriksson
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
authors.affiliation: Department of Pediatrics and Microbiology, Albert Einstein College of Medicine, New York, USA.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
authors.affiliation: Department of Cellular and Molecular Medicine, Centre for Glycomics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandall
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0002-0270-3602
authors.initials: S
authors.lastname: Frische
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Holm
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Søren R
authors.identifier: http://orcid.org/0000-0001-9180-4060
authors.initials: SR
authors.lastname: Paludan
mesh_terms: D000818:Animals; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006031:Glycosylation; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
chemical_list: D054357:Chemokine CXCL10; D008024:Ligands; D011134:Polysaccharides; D054367:Receptors, CXCR3; D014759:Viral Envelope Proteins; D007372:Interferons