In humans, psychological stress has been associated with a higher risk of infectious illness. However, the mechanisms by which the stress pathway interferes with host response to pathogens remain unclear. We demonstrate here a role for the β2-adrenergic receptor (β2-AR), which binds the stress mediators adrenaline and noradrenaline, in modulating host response to mouse cytomegalovirus (MCMV) infection. Mice treated with a β2-AR agonist were more susceptible to MCMV infection. By contrast, β2-AR deficiency resulted in a better clearance of the virus, less tissue damage, and greater resistance to MCMV. Mechanistically, we found a correlation between higher levels of IFN-γ production by liver natural killer (NK) cells and stronger resistance to MCMV. However, the control of NK cell IFN-γ production was not cell intrinsic, revealing a cell-extrinsic downregulation of the antiviral NK cell response by adrenergic neuroendocrine signals. This pathway reduces host immune defense, suggesting that the blockade of the β2-AR signaling could be used to increase resistance to infectious diseases.

中文翻译：

---

β2-肾上腺素能信号下调先天免疫反应并降低宿主对病毒感染的抵抗力

对于人类来说，心理压力与感染性疾病的较高风险有关。然而，应激途径干扰宿主对病原体反应的机制仍不清楚。我们在此证明了β2-肾上腺素受体（β2-AR）在调节宿主对小鼠巨细胞病毒（MCMV）感染的反应中的作用，它与应激介质肾上腺素和去甲肾上腺素结合。用 β2-AR 激动剂治疗的小鼠更容易受到 MCMV 感染。相比之下，β2-AR 缺陷可以更好地清除病毒、减少组织损伤以及增强对 MCMV 的抵抗力。从机制上讲，我们发现肝脏自然杀伤 (NK) 细胞产生的 IFN-γ 水平较高与对 MCMV 的抵抗力较强之间存在相关性。然而，NK 细胞 IFN-γ 产生的控制不是细胞内在的，这揭示了肾上腺素能神经内分泌信号对抗病毒 NK 细胞反应的细胞外源性下调。该途径降低了宿主的免疫防御，表明β2-AR信号传导的阻断可用于增强对传染病的抵抗力。