The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex

Abstract
Article and author information
Metrics

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

Sarah Stratmann

University of groningen, Groningen, Netherlands

Competing interests
No competing interests declared.
Seamus Morrone

Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
No competing interests declared.
Antoine M van Oijen

University of Groningen, Groningen, Netherlands

Competing interests
Antoine M van Oijen, Reviewing editor, eLife.
Jungsan Sohn

Johns Hopkins School of Medicine, Baltimore, United States

For correspondence
jsohn@jhmi.edu

Competing interests
No competing interests declared.

Copyright

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.