Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling.
Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling.
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DOI：
10.1093/infdis/jit824
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发表时间：
2014-06-01
期刊：
影响因子：
--
通讯作者：
Naglik JR
中科院分区：
文献类型：
--
作者：
Moyes DL;Shen C;Murciano C;Runglall M;Richardson JP;Arno M;Aldecoa-Otalora E;Naglik JR
背景： 是一种上皮细胞(ECs)区分共生微生物和致病微生物的能力，对健康生活至关重要。这些相互作用的关键是粘膜上皮对病原体诱导的损伤的反应。方法： 利用重组的口腔上皮，我们用微阵列技术评估了上皮细胞基因转录对白色念珠菌感染的反应。用Western blotting和转录因子酶联免疫吸附试验检测信号通路的激活情况，并用化学抑制剂检测这些信号通路在白念珠菌损伤保护中的作用。结果： 转录图谱显示参与免疫反应的上皮基因早期上调。其中许多基因构成了信号通路的组成部分，但只有NF-κB、MAPK和PI3K/Akt通路被功能性激活。我们证明PI3K/AKT信号不依赖于NF-κB和MAPK信号，并且通过哺乳动物雷帕霉素(MTor)的激活靶点在上皮免疫激活和损伤保护中发挥关键作用。结论： PI3K/AKT/MTOR信号可能在黏膜真菌感染中保护上皮细胞免受损害方面发挥关键作用，而不依赖于NF-κB或MAPK信号。
Background. The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage. Methods. Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans–induced damage protection was determined using chemical inhibitors. Results. Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation. Conclusions. PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling.
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