Farnesol promotes epithelial cell defense against Candida albicans through Toll-like receptor 2 expression, interleukin-6 and human β-defensin 2 production
Farnesol promotes epithelial cell defense against Candida albicans through Toll-like receptor 2 expression, interleukin-6 and human β-defensin 2 production
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DOI：
10.1016/j.cyto.2008.11.011
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发表时间：
2009-02-01
期刊：
影响因子：
3.8
通讯作者：
Rouabhia, Mahmoud
中科院分区：
文献类型：
--
作者：
Decanis, Nadege;Savignac, Katia;Rouabhia, Mahmoud
法尼醇是一种群体感应分子，调节白色念珠菌的毒力和形态发生，并参与包括口腔念珠菌病在内的各种人类病理。口腔上皮细胞通过toll样受体（TLRs）和炎症介质参与抗念珠菌感染的先天免疫。我们通过研究TLR2、4和6的表达，探讨了法尼醇对宿主细胞的影响及其与牙龈上皮细胞对抗白色念珠菌感染的协同作用。用工程人口腔黏膜组织与不同浓度的法尼醇接触，检测白细胞介素6、白细胞介素8和人β -防御素1和2的产生，有和没有白色念珠菌。我们的研究结果表明，与白色念珠菌接触24小时后，上皮细胞比未感染的细胞表达更多的TLR2。在白色念珠菌存在或不存在的情况下，外源性法尼醇的加入上调了牙龈上皮细胞TLR2的表达。相比之下，当将法尼醇添加到有或没有白色念珠菌的组织中时，TLR4下调。最后，单独使用法尼醇对TLR6没有影响，但在白色念珠菌和法尼醇同时存在时，TLR6的表达下调。法尼醇通过与白色念珠菌接触的上皮细胞调节TLR2的表达。这种作用与il - 6而非IL-8的分泌相似。法尼醇对先天免疫的作用因其能增加人β -防御素2的产生和β -防御素抑制白色念珠菌生长的功效而得到加强。总体结果表明，外源性法尼醇通过TLR2、IL-6和人β -防御素2的参与，促进了上皮细胞对白色念珠菌感染的防御。(C) 2008 Elsevier Ltd版权所有。
Farnesol, a quorum-sensing molecule, regulates virulence and morphogenesis in Candida albicans and is involved in various human pathologies including oral candidiasis. Oral epithelial cells are involved in innate immunity against Candida infections via Toll-like receptors (TLRs) and inflammatory mediators. We investigated the effects of farnesol on host cells and its possible synergistic interaction with gingival epithelial cells against C. albicans infection by studying the expression of TLR2, 4 and 6. The production of IL-6, IL-8, and human beta-defensins 1 and 2 was also examined using engineered human oral mucosa tissue put in contact with various concentrations of farnesol with and without C. albicans. Our findings indicate that 24 h after contact with C. albicans, epithelial cells expressed more TLR2 than did non-infected cells. The addition of exogenous farnesol upregulated the TLR2 expression by the gingival epithelial cells in the presence or absence of C. albicans. In contrast, TLR4 was down regulated when farnesol was added to the tissue with or without C albicans. Finally, farnesol alone was shown to have no effect on TLR6, yet in the presence of both C. albicans and farnesol, TLR6 expression was down regulated. Farnesol modulated TLR2 expression by the epithelial cells following tissue contact with C albicans. This effect was paralleled by IL6 but not IL-8 secretion. Farnesol's effect on innate immunity was strengthened by its capacity to increase human beta-defensin 2 production, and by the efficacy of beta-defensin against C albicans growth. Overall results showed that exogenous farnesol promoted epithelial cell defense against C. albicans infection through the involvement of TLR2, IL-6, and human beta-defensin 2. (C) 2008 Elsevier Ltd. All rights reserved.