Extensive evolutionary and functional diversity among mammalian AIM2-like receptors

Author:

Brunette Rebecca L.1,Young Janet M.2,Whitley Deborah G.1,Brodsky Igor E.3,Malik Harmit S.22,Stetson Daniel B.1

Affiliation:

1. Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195

2. Division of Basic Sciences and Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

3. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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