title: The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
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.
authors: Department of Immunology, University of Washington School of Medicine, Seattle, WA, 98195, USA.
authors: Elizabeth E
authors: EE
authors: Gray
authors: Department of Immunology, University of Washington School of Medicine, Seattle, WA, 98195, USA.
authors: Damion
authors: D
authors: Winship
authors: Department of Comparative Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA.
authors: Jessica M
authors: JM
authors: Snyder
authors: Departments of Microbiology and Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: Stephanie J
authors: SJ
authors: Child
authors: Departments of Microbiology and Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: Adam P
authors: AP
authors: Geballe
authors: Department of Immunology, University of Washington School of Medicine, Seattle, WA, 98195, USA. Electronic address: stetson@uw.edu.
authors: Daniel B
authors: DB
authors: Stetson
mesh_terms: D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology*; D002460:Cell Line; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005090:Exodeoxyribonucleases / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D016086:Lentivirus / Q000276:immunology*; D016180:Lentivirus Infections / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009421:Nervous System Malformations / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000099197:STING Protein
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D005090:Exodeoxyribonucleases; D007370:Interferon Type I; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C540422:Aim2 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein; C076700:IFI16 protein, human; C429526:three prime repair exonuclease 1