The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA

Immunity. 2016 Aug 16;45(2):255-66. doi: 10.1016/j.immuni.2016.06.015. Epub 2016 Aug 2.

Abstract

Detection of intracellular DNA triggers activation of the STING-dependent interferon-stimulatory DNA (ISD) pathway, which is essential for antiviral responses. Multiple DNA sensors have been proposed to activate this pathway, including AIM2-like receptors (ALRs). Whether the ALRs are essential for activation of this pathway remains unknown. To rigorously explore the function of ALRs, we generated mice lacking all 13 ALR genes. We found that ALRs are dispensable for the type I interferon (IFN) response to transfected DNA ligands, DNA virus infection, and lentivirus infection. We also found that ALRs do not contribute to autoimmune disease in the Trex1(-/-) mouse model of Aicardi-Goutières Syndrome. Finally, CRISPR-mediated disruption of the human AIM2-like receptor IFI16 in primary fibroblasts revealed that IFI16 is not essential for the IFN response to human cytomegalovirus infection. Our findings indicate that ALRs are dispensable for the ISD response and suggest that alternative functions for these receptors should be explored.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases of the Nervous System / immunology*
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • DNA / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease Models, Animal
  • Exodeoxyribonucleases / genetics
  • Genetic Loci / genetics
  • Humans
  • Interferon Type I / metabolism
  • Lentivirus / immunology*
  • Lentivirus Infections / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nervous System Malformations / immunology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*

Substances

  • Aim2 protein, mouse
  • DNA-Binding Proteins
  • Interferon Type I
  • MPYS protein, mouse
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • IFI16 protein, human
  • DNA
  • Exodeoxyribonucleases
  • three prime repair exonuclease 1

Supplementary concepts

  • Aicardi-Goutieres syndrome