Animal cells use pattern-recognition receptors (PRRs) to detect specific pathogens. Pathogen detection mounts an appropriate immune response, including interferon and cytokine induction. The intracellular PRR-signaling pathways that detect DNA viruses have been characterized, particularly in myeloid cells. In these pathways, cGMP-AMP synthase (cGAS) and the pyrin and HIN domain family member (PYHIN) protein interferon g-inducible protein 16 (IFI16) detect DNA and signal via stimulator of interferon genes protein (STING). However, although airway epithelial cells are frontline sentinels in detecting pathogens, information on how they respond to DNA viruses is limited, and the roles of PYHIN proteins in these cells are unknown. Here, we examined expression and activities of cGAS, STING, and PYHINs in human lung epithelial cells. A549 epithelial cells, commonly used for RNA-sensing studies, failed to respond to DNA because they lacked STING expression, and ectopic STING expression restored a cGAS-dependent DNA response in these cells. In contrast, NuLi-1 immortalized human bronchial epithelial cells did express STING, which was activated after DNA stimulation and mediated DNA-dependent gene induction. PYHIN1, which like IFI16 has been proposed to be a viral DNA sensor, was the only PYHIN protein expressed in both airway epithelial cell types. However, rather than having a role in DNA sensing, PYHIN1 induced proinflammatory cytokines in response to interleukin-1 (IL-1) or tumor necrosis factor α (TNF-α) stimulation. Of note, PYHIN1, via its HIN domain, directly induced IL-6 and TNF-α transcription, revealing that PYHIN proteins play a role in proinflammatory gene induction in airway epithelial cells.

中文翻译：

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PYHIN1调节促炎性细胞因子的诱导，而不是气道上皮细胞中的先天免疫DNA感应。

动物细胞使用模式识别受体（PRR）来检测特定的病原体。病原体检测可引起适当的免疫反应，包括干扰素和细胞因子的诱导。检测DNA病毒的细胞内PRR信号通路已被表征，尤其是在髓样细胞中。在这些途径中，cGMP-AMP合酶（cGAS）和pyrin和HIN域家族成员（PYHIN）蛋白干扰素g诱导蛋白16（IFI16）通过干扰素基因蛋白（STING）的刺激物检测DNA和信号。然而，尽管气道上皮细胞是检测病原体的一线哨兵，但有关它们如何对DNA病毒做出反应的信息仍然有限，而且PYHIN蛋白在这些细胞中的作用尚不清楚。在这里，我们检查了人肺上皮细胞中cGAS，STING和PYHIN的表达和活性。通常用于RNA传感研究的A549上皮细胞无法对DNA做出反应，因为它们缺乏STING表达，而异位STING表达恢复了这些细胞中cGAS依赖性的DNA反应。相反，NuLi-1永生化的人支气管上皮细胞确实表达了STING，STING在DNA刺激和介导的DNA依赖性基因诱导后被激活。像IFI16一样，PYHIN1也被认为是一种病毒DNA传感器，是两种气道上皮细胞类型中唯一表达的PYHIN蛋白。但是，PYHIN1不是在DNA感应中起作用，而是响应白介素1（IL-1）或肿瘤坏死因子α（TNF-α）刺激而诱导促炎性细胞因子。值得注意的是，PYHIN1通过其HIN域直接诱导IL-6和TNF-α转录，