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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.

SUBMITTER: Brunette RL

PROVIDER: S-EPMC3478938 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Extensive evolutionary and functional diversity among mammalian AIM2-like receptors.

Brunette Rebecca L RL Young Janet M JM Whitley Deborah G DG Brodsky Igor E IE Malik Harmit S HS Stetson Daniel B DB

The Journal of experimental medicine 20121008 11

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 receptor ...[more]

PMID: 23045604

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