细胞质DNA是先天免疫系统的一个重要触发器。这一过程中所涉及的下游信号通道已被广泛定性，但人们对其第一步、即DNA的识别却知之甚少。
现在，在本期Nature上发表论文的两个小组发现AIM2 (absent in melanoma 2) （“干扰素可诱导的HIN-200”家族的一个成员）是一个细胞质DNA传感器。在有DNA存在时，AIM2发生寡聚，并与衔接分子ASC结合来激发NF-κB 和半胱天冬酶-1——炎性体复合物的关键成分。这说明AIM2炎性体是治疗传染病和自体免疫疾病的一个可能的目标。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 458, 509-513 (26 March 2009) | doi:10.1038/nature07710
AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Teresa Fernandes-Alnemri1,2, Je-Wook Yu1,2, Pinaki Datta1, Jianghong Wu1 & Emad S. Alnemri1
1 Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
2 These authors contributed equally to this work.
Host- and pathogen-associated cytoplasmic double-stranded DNA triggers the activation of a NALP3 (also known as cryopyrin and NLRP3)-independent inflammasome1, which activates caspase-1 leading to maturation of pro-interleukin-1 and inflammation. The nature of the cytoplasmic-DNA-sensing inflammasome is currently unknown. Here we show that AIM2 (absent in melanoma 2), an interferon-inducible HIN-200 family member that contains an amino-terminal pyrin domain and a carboxy-terminal oligonucleotide/oligosaccharide-binding domain2, 3, senses cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain and interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1. The interaction of AIM2 with ASC also leads to the formation of the ASC pyroptosome4, which induces pyroptotic cell death in cells containing caspase-1. Knockdown of AIM2 by short interfering RNA reduced inflammasome/pyroptosome activation by cytoplasmic DNA in human and mouse macrophages, whereas stable expression of AIM2 in the non-responsive human embryonic kidney 293T cell line conferred responsiveness to cytoplasmic DNA. Our results show that cytoplasmic DNA triggers formation of the AIM2 inflammasome by inducing AIM2 oligomerization. This study identifies AIM2 as an important inflammasome component that senses potentially dangerous cytoplasmic DNA, leading to activation of the ASC pyroptosome and caspase-1.
