Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways.
Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways.
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DOI：
10.1159/000525315
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
呼吸道甲型流感病毒（IAV）感染继续对包括哮喘在内的人类疾病的医疗保健构成重大挑战。小鼠中的IAV感染显示出增加IL-33，这是驱动哮喘气道炎症的关键细胞因子，但在病毒感染期间IL-33如何调节仍不清楚。我们以前发现Toll相互作用蛋白（Tollip）的基因突变与哮喘患者气道上皮Tollip表达减少、中性粒细胞趋化因子增加和肺功能降低有关。由于Tollip参与维持线粒体功能，并且线粒体应激可能有助于细胞外ATP释放和IL-33分泌，因此我们假设Tollip通过抑制IAV感染期间的ATP释放来下调IL-33分泌。用IAV感染野生型和Tollip敲除（KO）小鼠，并用ATP转化体腺苷三磷酸双磷酸酶或IL-33诱饵受体可溶性ST 2（sST 2）处理。KO小鼠体重显著减轻，细胞外ATP、IL-33释放和嗜酸性炎症增加。腺苷三磷酸双磷酸酶处理降低了Tollip KO小鼠的细胞外ATP水平、IL-33释放和嗜酸性炎症。在IAV感染的Tollip KO小鼠中，过度的肺部嗜酸性炎症被sST 2减少，这与较少的IL-33释放相结合。我们的数据表明，Tollip抑制IAV感染，可能是通过抑制细胞外ATP释放和减少IL-33激活和肺部炎症。此外，sST 2可以作为一种潜在的治疗方法来减轻Tollip缺乏症人类受试者的呼吸道病毒感染。
Respiratory influenza A virus (IAV) infection continues to pose significant challenges in healthcare of human diseases including asthma. IAV infection in mice was shown to increase IL-33, a key cytokine in driving airway inflammation in asthma, but how IL-33 is regulated during viral infection remains unclear. We previously found that a genetic mutation in Toll-interacting protein (Tollip) was linked to less airway epithelial Tollip expression, increased neutrophil chemokines, and lower lung function in asthma patients. As Tollip is involved in maintaining mitochondrial function, and mitochondrial stress may contribute to extracellular ATP release and IL-33 secretion, we hypothesized that Tollip downregulates IL-33 secretion via inhibiting ATP release during IAV infection. Wild-type and Tollip knockout (KO) mice were infected with IAV and treated with either an ATP converter apyrase or an IL-33 decoy receptor soluble ST2 (sST2). KO mice significantly lost more body weight and had increased extracellular ATP, IL-33 release, and neutrophilic inflammation. Apyrase treatment reduced extracellular ATP levels, IL-33 release, and neutrophilic inflammation in Tollip KO mice. Excessive lung neutrophilic inflammation in IAV-infected Tollip KO mice was reduced by sST2, which was coupled with less IL-33 release. Our data suggest that Tollip inhibits IAV infection, potentially by inhibiting extracellular ATP release and reducing IL-33 activation and lung inflammation. In addition, sST2 may serve as a potential therapeutic approach to mitigate respiratory viral infection in human subjects with Tollip deficiency.
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影响因子：
9
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1003020
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
通讯作者：
Kita H
影响因子：
5.8
作者：
Boxio R;Wartelle J;Nawrocki-Raby B;Lagrange B;Malleret L;Hirche T;Taggart C;Pacheco Y;Devouassoux G;Bentaher A
通讯作者：
Bentaher A
影响因子：
5.7
作者：
Duan, Lihua;Chen, Jie;Fang, Min
通讯作者：
Fang, Min
支气管上皮细胞中的流感H5N1和H1N1病毒复制和先天免疫反应受分化状态的影响。
影响因子：
3.7
作者：
Chan RW;Yuen KM;Yu WC;Ho CC;Nicholls JM;Peiris JS;Chan MC
通讯作者：
Chan MC