Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages.
Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages.
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DOI：
10.1038/s41598-017-11012-7
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发表时间：
2017-09-07
影响因子：
4.6
通讯作者：
Bruscia EM
中科院分区：
文献类型：
--
作者：
Di Pietro C;Zhang PX;O'Rourke TK;Murray TS;Wang L;Britto CJ;Koff JL;Krause DS;Egan ME;Bruscia EM
在囊性纤维化跨膜传导调节因子（CFTR）中具有突变的巨噬细胞（MΦ）响应于TLR 4活化而钝化PI 3 K/AKT信号传导的诱导，导致炎症过度，这是囊性纤维化（CF）疾病的标志。在这里，我们表明Ezrin连接CFTR和TLR 4信号传导，并且是响应于MΦ活化的PI 3 K/AKT信号传导诱导所必需的。因为PI 3 K/AKT信号传导对于免疫调节是关键的，所以Ezrin缺陷的MΦ是高度炎症的并且具有受损的铜绿假单胞菌吞噬作用，表型化CF MΦ。重要的是，我们表明活化的CF MΦ具有降低的蛋白质水平和改变的剩余Ezrin在活化期间形成的丝状伪足的定位。总之，我们已经描述了从CFTR到Ezrin到PI 3 K/AKT信号传导的直接联系，其在CF中被破坏，从而促进过度炎症并减弱吞噬作用。
Macrophages (MΦs) with mutations in cystic fibrosis transmembrane conductance regulator (CFTR) have blunted induction of PI3K/AKT signaling in response to TLR4 activation, leading to hyperinflammation, a hallmark of cystic fibrosis (CF) disease. Here, we show that Ezrin links CFTR and TLR4 signaling, and is necessary for PI3K/AKT signaling induction in response to MΦ activation. Because PI3K/AKT signaling is critical for immune regulation, Ezrin-deficient MΦs are hyperinflammatory and have impaired Pseudomonas aeruginosa phagocytosis, phenocopying CF MΦs. Importantly, we show that activated CF MΦs have reduced protein levels and altered localization of the remaining Ezrin to filopodia that form during activation. In summary, we have described a direct link from CFTR to Ezrin to PI3K/AKT signaling that is disrupted in CF, and thus promotes hyper-inflammation and weakens phagocytosis.
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影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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