Yano J, Lilly E A, Steele C, Fortenberry D, Fidel P L
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, 70112, USA.
Oral Microbiol Immunol. 2005 Aug;20(4):199-205. doi: 10.1111/j.1399-302X.2005.00212.x.
Candida albicans is the causative agent of oral and vaginal candidiasis. Innate host defenses against C. albicans are important against each infection. Among these are oral and vaginal epithelial cells that have anti-Candida activity. The mechanism of action includes a requirement for cell contact with no role for soluble factors, and a putative role for carbohydrates based on the sensitivity of the activity to periodic acid.
Periodic acid treatment of epithelial cells as well as the property of partial resistance of antifungal activity to fixation was used to further dissect the mechanism of action.
The results herein effectively now challenge a role for carbohydrates alone. Firstly, the putative carbohydrate(s) released into supernatants of periodic acid-treated epithelial cells could not compete with fresh epithelial cells for activity, and equivalent abrogation of activity was observed by periodic acid-treated cells irrespective of the amount of carbohydrate released. Instead, the similar abrogation of activity following treatment with other acids or when cocultured under acidic conditions suggests that the activity is acid-labile. Finally, while activity requires intact epithelial cells, it does not require live cells; activity was minimally affected by fixing epithelial cells prior to coculture where the majority of cells remained impermeable to Trypan blue but were defined as non-viable by positive nuclear staining with propidium iodide.
These results suggest that antifungal activity is dependent on contact by intact, but not necessarily live, epithelial cells through an acid-labile mechanism.
白色念珠菌是口腔和阴道念珠菌病的病原体。宿主对白色念珠菌的固有防御对于抵抗每种感染都很重要。其中包括具有抗念珠菌活性的口腔和阴道上皮细胞。其作用机制包括细胞接触的必要性,可溶性因子不起作用,以及基于该活性对高碘酸的敏感性推测碳水化合物起作用。
使用高碘酸处理上皮细胞以及抗真菌活性对固定的部分抗性特性来进一步剖析作用机制。
本文的结果现在有效地挑战了仅碳水化合物起作用的观点。首先,释放到高碘酸处理的上皮细胞上清液中的假定碳水化合物不能与新鲜上皮细胞竞争活性,并且无论释放的碳水化合物量如何,高碘酸处理的细胞都观察到等效的活性消除。相反,用其他酸处理后或在酸性条件下共培养时观察到类似的活性消除,这表明该活性对酸不稳定。最后,虽然活性需要完整的上皮细胞,但不需要活细胞;在共培养前固定上皮细胞时活性受到的影响最小,此时大多数细胞对台盼蓝仍不渗透,但通过碘化丙啶阳性核染色被定义为无活力。
这些结果表明,抗真菌活性取决于完整但不一定是活的上皮细胞通过酸不稳定机制的接触。