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真菌群体感应分子法呢醇调节阴道上皮细胞对白色念珠菌的免疫反应。

The fungal quorum-sensing molecule, farnesol, regulates the immune response of vaginal epithelial cells against Candida albicans.

机构信息

Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.

Department of Microecological Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.

出版信息

BMC Microbiol. 2023 Sep 8;23(1):251. doi: 10.1186/s12866-023-02987-7.

DOI:10.1186/s12866-023-02987-7
PMID:37684571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10485994/
Abstract

BACKGROUND

Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis, especially vulvovaginal candidiasis (VVC).

METHODS

The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes.

RESULTS

Only low concentrations (≤ 50 µmol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05).

CONCLUSIONS

Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.

摘要

背景

法尼醇是一种酵母菌分泌的群体感应分子,作为一种有潜力的抗真菌药物,对严重且难以治愈的感染(念珠菌病,特别是阴道念珠菌病(VVC))具有很大的吸引力。

方法

评估了法尼醇对细胞形态和活力的影响,并评估了法尼醇对阴道上皮细胞系(VK2)培养上清液中 Th1(IL-2)、Th2(IL-4)、促炎(IL-6)、趋化(IL-8)和 Th17(IL-17)细胞因子产生的影响。此外,我们还测试了法尼醇对 C. albicans 黏附的抑制作用。进行扫描电子显微镜观察以观察 VK2 细胞的任何超微结构变化。

结果

只有低浓度(≤50μmol/L)的法尼醇不会影响 VK2 细胞的形态和活力(P>0.05)。法尼醇降低了 C. albicans 对 VK2 细胞的黏附。用法尼醇处理后,感染 VK2 细胞分泌的 IL-4 和 IL-17 水平均显著升高(P<0.05)。

结论

法尼醇作为一种刺激物,可上调 C. albicans 感染后的 Th17 型固有免疫反应以及 Th2 型体液免疫。需要进一步研究以选择最佳治疗剂量,开发有效的、安全的黏膜免疫佐剂来治疗 VVC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/00354a72889c/12866_2023_2987_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/10ac18d7cc87/12866_2023_2987_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/015c6de00c0f/12866_2023_2987_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/09d940f11d3d/12866_2023_2987_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/7bd7f0a62e36/12866_2023_2987_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/00354a72889c/12866_2023_2987_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/10ac18d7cc87/12866_2023_2987_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/015c6de00c0f/12866_2023_2987_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/09d940f11d3d/12866_2023_2987_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/7bd7f0a62e36/12866_2023_2987_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/10485994/00354a72889c/12866_2023_2987_Fig5_HTML.jpg

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本文引用的文献

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Mycoses. 2021 Jun;64(6):583-602. doi: 10.1111/myc.13248. Epub 2021 Feb 27.
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Inhibiting roles of farnesol and HOG in morphological switching of .法尼醇和高渗甘油应答(HOG)途径在……形态转换中的抑制作用 。 你提供的原文似乎不完整,“Inhibiting roles of farnesol and HOG in morphological switching of.”后面缺少具体内容。
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Pharmacological applications of farnesol (CHO): a patent review.法呢醇(CHO)的药理学应用:专利审查。
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Vaginal Epithelial Cells Discriminate Between Yeast and Hyphae of Candida albicans in Women Who Are Colonized or Have Vaginal Candidiasis.阴道上皮细胞可区分定植或患有阴道念珠菌病女性的白色念珠菌的酵母相和菌丝相。
J Infect Dis. 2019 Oct 8;220(10):1645-1654. doi: 10.1093/infdis/jiz365.
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Regulation of Virulence.毒力调控
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