Marie B Iversen1,2, Line S Reinert1,2,12, Martin K Thomsen1,2,12, Ieva Bagdonaite3, Ramya Nandakumar1,2, Natalia Cheshenko4, Thaneas Prabakaran1,2, Sergey Y Vakhrushev3, Malgosha Krzyzowska5, Sine K Kratholm1,2, Fernando Ruiz-Perez6, Steen V Petersen1, Stanislas Goriely7, Bo Martin Bibby8, Kristina Eriksson9, Jürgen Ruland10, Allan R Thomsen11, Betsy C Herold4, Hans H Wandall3, Sebastian Frische1, Christian K Holm1,2,13 & Søren R Paludan1,2,13
Nature Immunology (2015) doi:10.1038/ni.3319
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.
1Department of Biomedicine, University of Aarhus, Aarhus, Denmark. 2Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark. 3Department of Cellular and Molecular Medicine, Centre for Glycomics, University of Copenhagen, Copenhagen, Denmark. 4Department of Pediatrics and Microbiology, Albert Einstein College of Medicine, New York, USA. 5Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland. 6Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, USA. 7Institute for Medical Immunology, UniversitÃ© Libre de Bruxelles, Gosselies, Belgium. 8Department of Biostatistics, University of Aarhus, Aarhus, Denmark. 9Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden. 10Institut fÃ¼r Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische UniversitÃ¤t MÃ¼nchen, Munich, Germany. 11Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.