Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates.
Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates.
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DOI：
10.7554/elife.61241
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发表时间：
2021-03-02
期刊：
影响因子：
7.7
通讯作者：
Sengupta S
中科院分区：
文献类型：
--
作者：
Issah Y;Naik A;Tang SY;Forrest K;Brooks TG;Lahens N;Theken KN;Mermigos M;Sehgal A;Worthen GS;FitzGerald GA;Sengupta S
不良的生命早期暴露对健康有持久的负面影响。新生儿高氧是支气管肺发育不良的一个危险因素，会使生命后期对甲型流感病毒（IAV）感染具有易感性。鉴于我们之前的发现，即生物钟可预防IAV，我们询问新生儿高氧相对于IAV感染的长期影响是否包括生物钟紊乱。在此，我们表明新生儿高氧消除了小鼠体内生物钟介导的对IAV的每日时间保护作用，且这种作用与通过宿主耐受途径的病毒载量无关。我们发现肺内源性生物钟（而非中枢或免疫生物钟）介导了这种失调。肺泡Ⅱ型（AT2）细胞中生物钟蛋白Bmal1的缺失重现了高氧暴露动物的死亡率增加、时间门控丧失以及其他关键特征。我们的数据表明，生物钟在AT2细胞中在介导生命早期暴露对肺的长期影响方面具有一种新的作用。
Adverse early-life exposures have a lasting negative impact on health. Neonatal hyperoxia that is a risk factor for bronchopulmonary dysplasia confers susceptibility to influenza A virus (IAV) infection later in life. Given our previous findings that the circadian clock protects against IAV, we asked if the long-term impact of neonatal hyperoxia vis-à-vis IAV infection includes circadian disruption. Here, we show that neonatal hyperoxia abolishes the clock-mediated time of day protection from IAV in mice, independent of viral burden through host tolerance pathways. We discovered that the lung intrinsic clock (and not the central or immune clocks) mediated this dysregulation. Loss of circadian protein, Bmal1, in alveolar type 2 (AT2) cells recapitulates the increased mortality, loss of temporal gating, and other key features of hyperoxia-exposed animals. Our data suggest a novel role for the circadian clock in AT2 cells in mediating long-term effects of early-life exposures to the lungs.
影响因子：
3.3
作者：
Adler, D. A.;Ammanuel, S.;Lei, J.;Dada, T.;Borbiev, T.;Johnston, M. V.;Kadam, S. D.;Burd, I.
通讯作者：
Burd, I.