Defective interferon amplification and impaired host responses against influenza virus in obese mice
Defective interferon amplification and impaired host responses against influenza virus in obese mice
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DOI：
10.1002/oby.23196
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发表时间：
2021-08-01
期刊：
影响因子：
6.9
通讯作者：
Wirth, Dagmar
中科院分区：
文献类型：
--
作者：
Gaur, Pratibha;Riehn, Mathias;Wirth, Dagmar
目的肥胖是增加感染后发病率和死亡率的主要危险因素。尽管I型和III型干扰素（IFN）诱导的先天免疫反应是抵御病毒感染的第一道防线，但它们在代谢紊乱中的功能在很大程度上仍不清楚。本研究旨在探讨IFN对肥胖小鼠呼吸道病毒感染的反应。方法观察高脂喂养小鼠感染H3N2流感后IFN及IFN调节因子（IRFs）的激活情况。结果肥胖小鼠流感感染具有较高的死亡率。深入分析显示，I型和III型IFN诱导受损，IFN反应明显降低。值得注意的是，研究发现肥胖动物体内的IRF7基因表达在稳态状态下降低，病毒对其的诱导作用被强烈减弱。结论IRF7的表达减弱和诱导是导致I型和III型ifn表达水平降低的原因，从而导致肥胖小鼠对呼吸道感染的易感性和严重程度增加。
Objective Obesity is a major risk factor that increases morbidity and mortality upon infection. Although type I and type III interferon (IFN)-induced innate immune responses represent the first line of defense against viral infections, their functionality in the context of metabolic disorders remains largely obscure. This study aimed to investigate IFN responses upon respiratory viral infection in obese mice. Methods The activation of IFNs as well as IFN regulatory factors (IRFs) upon H3N2 influenza infection in mice upon high-fat-diet feeding was investigated. Results Influenza infection of obese mice was characterized by higher mortalities. In-depth analysis revealed impaired induction of both type I and type III IFNs as well as markedly reduced IFN responses. Notably, it was found that IRF7 gene expression in obese animals was reduced in homeostasis, and its induction by the virus was strongly attenuated. Conclusions The results suggest that the attenuated IRF7 expression and induction are responsible for the reduced expression levels of type I and III IFNs and, thus, for the higher susceptibility and severity of respiratory infections in obese mice.