Interleukin-1ß induces mitochondrial DAMP production to activate STING-dependent innate immune programs

Here we report that exogenous IL-1ß induces TBK1-mediated interferon regulatory factor 3 (IRF3) activation and autophagic flux in human myeloid and epithelial cells. IL-1ß-induced innate immune activation is dependent upon the DNA sensing pathway adaptor, stimulator of interferon genes (STING), through the recognition of mitochondrial DNA by cyclic GMP-AMP synthase (cGAS). Thus, IL-1ß potentiates pathogen-induced interferon production and signal transducer and activator of transcription (STAT) signaling to amplify innate immune responses. Overall design: A time series single cell RNA-seq analysis of interleukin-1ß-treated human alveolar epithelial cells.

本研究报道，外源性白细胞介素1β（IL-1β）可在人髓系细胞与上皮细胞中诱导TANK结合激酶1（TBK1）介导的干扰素调节因子3（IRF3）激活以及自噬流。白细胞介素1β诱导的天然免疫激活依赖于DNA感知通路接头蛋白干扰素基因刺激因子（STING），具体通过环鸟苷酸-腺苷酸合成酶（cGAS）识别线粒体DNA实现。因此，白细胞介素1β可增强病原体诱导的干扰素生成与信号转导与转录激活因子（STAT）信号通路活性，以放大天然免疫应答。整体实验设计：对经白细胞介素1β处理的人肺泡上皮细胞进行时序单细胞RNA测序分析。