Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin.

Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin.
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在流感感染期间,老年小鼠的NLRP3炎症功能受损是通过用粘霉素治疗挽救的。

DOI:
10.4049/jimmunol.1103051
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发表时间:
2012-03-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Harrod KS
Harrod KS
中科院分区:
其他
文献类型:
--
作者:
Stout-Delgado HW;Vaughan SE;Shirali AC;Jaramillo RJ;Harrod KS

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NLRP 3炎性小体在流感病毒感染期间在肺中被激活;然而,尚未检查流感感染期间老化对炎性小体功能的影响。在这里,我们发现,感染了小鼠适应流感病毒株的老年小鼠在体外和体内感染期间产生较低水平的IL-1β。与年轻感染小鼠相比,来自老年小鼠的树突状细胞表现出ASC、NLRP 3和半胱氨酸蛋白酶-1的表达降低,但pro-IL-1β、pro-IL-18和pro-IL-33的表达增加。在流感感染期间用尼日利亚菌素治疗增加了IL-1β的产生,增加了caspase-1的活性,并降低了老年小鼠的发病率和死亡率。我们的研究首次证明,在流感病毒感染期间,老年小鼠的NLRP 3炎性小体活性受损,并且用尼日利亚菌素治疗可以挽救老年宿主中的NLRP 3激活。
The NLRP3 inflammasome is activated in the lung during influenza viral infection; however the impact of aging on inflammasome function during influenza infection has not been examined. Here, we show that elderly mice infected with a mouse adapted strain of influenza produced lower levels of IL-1β during in vitro and in vivo infection. Dendritic cells from elderly mice exhibited decreased expression of ASC, NLRP3, and capase-1, but increased expression of pro-IL-1β, pro-IL-18, and pro-IL-33 when compared to young infected mice. Treatment with nigericin during influenza infection augmented IL-1β production, increased caspase-1 activity, and decreased morbidity and mortality in elderly mice. Our study demonstrates for the first time that during influenza viral infection, elderly mice have impaired NLRP3 inflammasome activity and that treatment with nigericin rescues NLRP3 activation in elderly hosts.
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