title: Extensive evolutionary and functional diversity among mammalian AIM2-like receptors.
abstract: Innate immune detection of nucleic acids is important for initiation of antiviral responses. Detection of intracellular DNA activates STING-dependent type I interferons (IFNs) and the ASC-dependent inflammasome. Certain members of the AIM2-like receptor (ALR) gene family contribute to each of these pathways, but most ALRs remain uncharacterized. Here, we identify five novel murine ALRs and perform a phylogenetic analysis of mammalian ALRs, revealing a remarkable diversification of these receptors among mammals. We characterize the expression, localization, and functions of the murine and human ALRs and identify novel activators of STING-dependent IFNs and the ASC-dependent inflammasome. These findings validate ALRs as key activators of the antiviral response and provide an evolutionary and functional framework for understanding their roles in innate immunity.
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Brunette
authors.forename: Janet M
authors.initials: JM
authors.lastname: Young
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Whitley
authors.forename: Igor E
authors.initials: IE
authors.lastname: Brodsky
authors.forename: Harmit S
authors.initials: HS
authors.lastname: Malik
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Stetson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000166:cytology; D019143:Evolution, Molecular; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008322:Mammals / Q000235:genetics*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D000099197:STING Protein
chemical_list: D004268:DNA-Binding Proteins; D058847:Inflammasomes; D007372:Interferons; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C540422:Aim2 protein, mouse; C489664:Ifi16 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein