Extensive evolutionary and functional diversity among mammalian AIM2-like receptors

• Published in: The Journal of experimental medicine Vol. 209; no. 11; pp. 1969 - 1983
• Main Authors: Brunette, Rebecca L., Young, Janet M., Whitley, Deborah G., Brodsky, Igor E., Malik, Harmit S., Stetson, Daniel B.
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 22.10.2012
• Subjects: Animals; Base Sequence; Cells, Cultured; DNA-Binding Proteins; Embryo, Mammalian - cytology; Evolution, Molecular; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression; Genetic Variation; HEK293 Cells; HeLa Cells; Humans; Inflammasomes - metabolism; Interferons - genetics; Interferons - metabolism; Mammals - genetics; Membrane Proteins - deficiency; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Nuclear Proteins - classification; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoproteins - classification; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phylogeny; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Sequence Homology, Nucleic Acid
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20121960

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.