The vagus nerve mediates parasympathetic nervous system control of peripheral physiological processes including cardiovascular activity and immune response. In mice, tonic vagal activation down-regulates inflammation via nicotinic acetylcholine receptor-mediated inhibition of the pro-inflammatory transcription factor NF-κB in monocyte/macrophages. Because Type I interferon and pro-inflammatory genes are regulated reciprocally at the level of transcription factor activation and cell differentiation, we hypothesized that vagal activity would up-regulate Type I interferon response genes concurrently with inflammatory downregulation in human immune cells. We mapped empirical individual differences in the circulating leukocyte transcriptome and vagal activity indexed by high frequency (0.15–0.40 Hz) heart rate variability (HF-HRV) in 380 participants in the Midlife in the US study. Here we show that promoter-based bioinformatics analyses linked greater HF-HRV to reduced NF-κB activity and increased activity of IRF transcription factors involved in Type I interferon response (independent of β-antagonists, BMI, smoking, heavy alcohol consumption, and demographic factors). Transcript origin analyses implicated myeloid lineage immune cells as targets, representing per-cell alterations in gene transcription as HF-HRV was not associated with differential prevalence of leukocyte subsets. These findings support the concept of parasympathetic inhibition of pro-inflammatory gene expression in humans and up-regulation of Type I interferons that could augment host defense against viral infections.

迷走神经介导副交感神经系统对周围生理过程的控制，包括心血管活动和免疫反应。在小鼠中，强直迷走神经激活通过烟碱乙酰胆碱受体介导的对单核细胞/巨噬细胞中促炎转录因子 NF-κB 的抑制来下调炎症。由于 I 型干扰素和促炎基因在转录因子激活和细胞分化水平上相互调节，我们假设迷走神经活动会上调 I 型干扰素反应基因，同时下调人类免疫细胞的炎症。我们绘制了美国研究中 380 名中年参与者的循环白细胞转录组和迷走神经活动的经验个体差异，以高频（0.15-0.40 Hz）心率变异性（HF-HRV）为索引。在这里，我们表明，基于启动子的生物信息学分析将更大的 HF-HRV 与 NF-κB 活性降低和参与 I 型干扰素反应的 IRF 转录因子活性增加联系起来（独立于 β-拮抗剂、BMI、吸烟、酗酒和人口统计）因素）。转录起源分析表明骨髓谱系免疫细胞作为靶标，代表每个细胞的基因转录变化，因为 HF-HRV 与白细胞亚群的差异流行率无关。这些发现支持副交感神经抑制人类促炎基因表达和上调 I 型干扰素的概念，从而增强宿主对病毒感染的防御能力。