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IFI16 is an innate immune sensor for intracellular DNA

Research output: Contribution to journalJournal article

Published
  • Leonie Unterholzner
  • Sinead E. Keating
  • Marcin Baran
  • Kristy A. Horan
  • Søren B. Jensen
  • Shruti Sharma
  • Cherilyn M. Sirois
  • Tengchuan Jin
  • Eicke Latz
  • T. Sam Xiao
  • Katherine A. Fitzgerald
  • Søren R. Paludan
  • Andrew G. Bowie
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<mark>Journal publication date</mark>11/2010
<mark>Journal</mark>Nature Immunology
Issue number11
Volume11
Number of pages8
Pages (from-to)997-1004
Publication StatusPublished
<mark>Original language</mark>English

Abstract

The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-β (IFN-β). IFI16 directly associated with IFN-β-inducing viral DNA motifs. STING, a critical mediator of IFN-β responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).