Circadian control of lung inflammation in influenza infection
Circadian control of lung inflammation in influenza infection
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DOI：
10.1038/s41467-019-11400-9
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发表时间：
2019-09-11
影响因子：
16.6
通讯作者：
FitzGerald, Garret A.
中科院分区：
文献类型：
--
作者：
Sengupta, Shaon;Tang, Soon Y.;FitzGerald, Garret A.
流感是呼吸道疾病死亡和发病的主要原因。虽然炎症对于对抗感染至关重要，但抗病毒防御和宿主耐受性的平衡对于恢复是必要的。昼夜节律已被证明可以调节炎症。然而，昼夜变化在流感感染时间的重要性还没有得到很好的理解。在这里，我们证明了内源性节律影响流感感染的生存。流感感染的昼夜节律控制由增强的炎症介导，如支气管肺泡灌洗（BAL）、肺转录组学特征和组织学中细胞结构增加所证明的，并且不归因于病毒负荷。较好的存活率与NK和NKT细胞的时间依赖性优势以及肺中炎性单核细胞的较低比例相关。此外，使用一系列的遗传小鼠突变体，我们阐明细胞机制的昼夜节律门控流感感染。
Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is essential for fighting infection, a balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms affect survival in influenza infection. Circadian control of influenza infection is mediated by enhanced inflammation as proven by increased cellularity in bronchoalveolar lavage (BAL), pulmonary transcriptomic profile and histology and is not attributable to viral burden. Better survival is associated with a time dependent preponderance of NK and NKT cells and lower proportion of inflammatory monocytes in the lung. Further, using a series of genetic mouse mutants, we elucidate cellular mechanisms underlying circadian gating of influenza infection.