Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
J Exp Med. 2012 Oct 22;209(11):1969-83. doi: 10.1084/jem.20121960. Epub 2012 Oct 8.
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.
先天免疫检测核酸对于启动抗病毒反应非常重要。检测细胞内 DNA 会激活 STING 依赖性 I 型干扰素 (IFN) 和 ASC 依赖性炎性体。AIM2 样受体 (ALR) 基因家族的某些成员有助于这两种途径，但大多数 ALR 仍未被描述。在这里，我们鉴定了五个新的鼠类 ALR，并对哺乳动物的 ALR 进行了系统发育分析，揭示了这些受体在哺乳动物中的显著多样化。我们描述了鼠类和人类 ALR 的表达、定位和功能，并确定了 STING 依赖性 IFN 和 ASC 依赖性炎性体的新激活剂。这些发现验证了 ALR 作为抗病毒反应的关键激活剂，并为理解它们在先天免疫中的作用提供了进化和功能框架。
