Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Eur J Immunol. 2019 Nov;49(11):1998-2011. doi: 10.1002/eji.201848070. Epub 2019 Aug 14.
AIM2 is a cytosolic innate immune receptor which recognizes double-stranded DNA (dsDNA) released during cellular perturbation and pathogenic assault. AIM2 recognition of dsDNA leads to the assembly of a large multiprotein oligomeric complex termed the inflammasome. This inflammasome assembly leads to the secretion of bioactive interleukin-1β (IL-1β) and IL-18 and induction of an inflammatory form of cell death called pyroptosis. Sensing of dsDNA by AIM2 in the cytosol is crucial to mediate protection against the invading pathogens including bacteria, virus, fungi and parasites. AIM2 also responds to dsDNA released from damaged host cells, resulting in the secretion of the effector cytokines thereby driving the progression of sterile inflammatory diseases such as skin disease, neuronal disease, chronic kidney disease, cardiovascular disease and diabetes. Additionally, the protection mediated by AIM2 in the development of colorectal cancer depends on its ability to regulate epithelial cell proliferation and gut microbiota in maintaining intestinal homeostasis independently of the effector cytokines. In this review, we will highlight the recent progress on the role of the AIM2 inflammasome as a guardian of cellular integrity in modulating chronic inflammatory diseases, cancer and infection.
AIM2 是一种细胞质先天免疫受体，可识别细胞扰动和病原体攻击过程中释放的双链 DNA（dsDNA）。AIM2 对 dsDNA 的识别导致一种称为炎性体的大型多蛋白寡聚复合物的组装。这种炎性体的组装导致生物活性白细胞介素-1β（IL-1β）和 IL-18 的分泌，并诱导称为细胞焦亡的炎症形式的细胞死亡。AIM2 在细胞质中对 dsDNA 的感应对于介导对入侵病原体（包括细菌、病毒、真菌和寄生虫）的保护至关重要。AIM2 还对来自受损宿主细胞释放的 dsDNA 作出反应，导致效应细胞因子的分泌，从而推动无菌性炎症性疾病（如皮肤病、神经疾病、慢性肾病、心血管疾病和糖尿病）的进展。此外，AIM2 在结直肠癌发展过程中的保护作用取决于其调节上皮细胞增殖和肠道微生物群的能力，以维持肠道内环境平衡，而不依赖于效应细胞因子。在这篇综述中，我们将重点介绍 AIM2 炎性体作为细胞完整性守护者在调节慢性炎症性疾病、癌症和感染方面的最新进展。
