An innate antiviral pathway acting before interferons at epithelial surfaces

Nat Immunol. 2016 Feb;17(2):150-8. doi: 10.1038/ni.3319. Epub 2015 Nov 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CXCL10 / biosynthesis
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Glycosylation
  • Herpes Simplex / genetics
  • Herpes Simplex / immunology
  • Herpes Simplex / metabolism
  • Herpes Simplex / virology
  • Herpesvirus 2, Human / immunology
  • Humans
  • Immunity, Innate*
  • Interferons / genetics
  • Interferons / metabolism*
  • Ligands
  • Mice
  • Mice, Knockout
  • Mucous Membrane / immunology*
  • Mucous Membrane / metabolism*
  • Mucous Membrane / virology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Polysaccharides / immunology
  • Receptors, CXCR3 / deficiency
  • Receptors, CXCR3 / metabolism
  • Vagina / immunology
  • Vagina / metabolism
  • Vagina / virology
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Load
  • Virus Diseases / immunology*
  • Virus Diseases / metabolism*
  • Virus Diseases / virology

Substances

  • Chemokine CXCL10
  • Ligands
  • Polysaccharides
  • Receptors, CXCR3
  • Viral Envelope Proteins
  • Interferons