1. Immunology and Inflammation
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The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex

  1. Sarah Stratmann
  2. Seamus Morrone
  3. Antoine M van Oijen
  4. Jungsan Sohn  Is a corresponding author
  1. University of groningen, Netherlands
  2. Johns Hopkins University School of Medicine, United States
  3. University of Groningen, Netherlands
  4. Johns Hopkins School of Medicine, United States
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Cite this article as: eLife 2015;4:e11721 doi: 10.7554/eLife.11721

Abstract

The ability to recognize foreign double-stranded (ds)DNA of pathogenic origin in the intracellular environment is an essential defense mechanism of the human innate immune system. However, the molecular mechanisms underlying distinction between foreign DNA and host genomic material inside the nucleus are not understood. By combining biochemical assays and single-molecule techniques, we show that the nuclear innate immune sensor IFI16 one-dimensionally tracks long stretches of exposed foreign dsDNA to assemble into supramolecular signaling platforms. We also demonstrate that nucleosomes represent barriers that prevent IFI16 from targeting host DNA by directly interfering with these one-dimensional movements. This unique scanning-assisted assembly mechanism allows IFI16 to distinguish friend from foe and assemble into oligomers efficiently and selectively on foreign DNA.

Article and author information

Author details

  1. Sarah Stratmann

    University of groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  2. Seamus Morrone

    Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
  3. Antoine M van Oijen

    University of Groningen, Groningen, Netherlands
    Competing interests
    Antoine M van Oijen, Reviewing editor, eLife.
  4. Jungsan Sohn

    Johns Hopkins School of Medicine, Baltimore, United States
    For correspondence
    jsohn@jhmi.edu
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. David M Knipe, Harvard Medical School, United States

Publication history

  1. Received: September 19, 2015
  2. Accepted: December 15, 2015
  3. Accepted Manuscript published: December 16, 2015 (version 1)
  4. Version of Record published: April 5, 2016 (version 2)

Copyright

© 2015, Stratmann et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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