Low ambient humidity impairs barrier function and innate resistance against influenza infection
Low ambient humidity impairs barrier function and innate resistance against influenza infection
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DOI：
10.1073/pnas.1902840116
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发表时间：
2019-05-28
影响因子：
11.1
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
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作者：
Kudo, Eriko;Song, Eric;Iwasaki, Akiko
在温带地区，季节性流感病毒的爆发与湿度的下降密切相关。虽然已知低环境湿度会增强病毒传播，但其对宿主对流感病毒感染的反应和疾病结果的影响仍不清楚。在这里，我们表明，住房Mx 1同源小鼠在低相对湿度使小鼠更容易受到严重的疾病后，呼吸挑战与流感病毒。我们发现，吸入干燥空气损害粘膜纤毛清除，先天性抗病毒防御和组织修复。此外，在caspase-1/11缺陷型Mx 1小鼠中，由低相对湿度加重的疾病得到改善，与病毒负荷无关。单细胞RNA测序显示，在低湿度条件下饲养的小鼠肺中的多种细胞类型中，IFN刺激的基因对病毒感染的反应的诱导减少。这些结果表明，暴露于干燥的空气损害宿主对流感感染的防御，减少组织修复，并造成半胱天冬酶依赖性疾病的病理。
In the temperate regions, seasonal influenza virus outbreaks correlate closely with decreases in humidity. While low ambient humidity is known to enhance viral transmission, its impact on host response to influenza virus infection and disease outcome remains unclear. Here, we showed that housing Mx1 congenic mice in low relative humidity makes mice more susceptible to severe disease following respiratory challenge with influenza A virus. We find that inhalation of dry air impairs mucociliary clearance, innate antiviral defense, and tissue repair. Moreover, disease exacerbated by low relative humidity was ameliorated in caspase-1/11-deficient Mx1 mice, independent of viral burden. Single-cell RNA sequencing revealed that induction of IFN-stimulated genes in response to viral infection was diminished in multiple cell types in the lung of mice housed in low humidity condition. These results indicate that exposure to dry air impairs host defense against influenza infection, reduces tissue repair, and inflicts caspase-dependent disease pathology.