A Novel Role for Histatin 5 in Combination with Zinc to Promote Commensalism in C. albicans Survivor Cells.
A Novel Role for Histatin 5 in Combination with Zinc to Promote Commensalism in C. albicans Survivor Cells.
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DOI：
10.3390/pathogens10121609
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发表时间：
2021-12-10
期刊：
影响因子：
--
通讯作者：
Edgerton M
中科院分区：
文献类型：
--
作者：
Norris HL;Kumar R;Edgerton M
白色念珠菌通过免疫机制维持在口腔上皮细胞中作为寄生虫。口服抗真菌肽Hst 5可能在天然免疫中发挥作用，但Hst 5在C.白色念珠菌感染尚不清楚。由于锌结合增强了Hst 5的杀念珠菌活性，我们假设Hst 5+Zn将引起一种独特的真菌应激反应，以形成C.白色念珠菌和口腔上皮细胞（OECs）。我们发现，Hst 5+Zn，而不是单独的Hst 5导致细胞壁完整性（CWI）信号的激活，然后使用缺失突变体来确定CWI介导的几丁质合成是保护性的杀伤。使用流式细胞术，我们证实，与Hst 5处理的细胞相比，Hst 5+ Zn处理的细胞具有显著升高的细胞壁几丁质、甘露聚糖和β-1，3葡聚糖水平。然后，我们测试了参与C.白色念珠菌细胞壁识别。免疫印迹法检测C.暴露于白色念珠菌的口腔上皮细胞显示EphA 2和NF-κB的活化增加，但EGFR没有增加。有趣的是，C。用Hst 5+Zn处理的白色念珠菌诱导从OECs释放促炎细胞因子的全面抑制，但增加负调节因子IL-10。Hst 5+ Zn处理的细胞比对照细胞更粘附，但最终对OECs的侵袭性更小，从而表明毒力降低。因此，Hst 5+ Zn处理的C. Hst 5+Zn联合应用可能对口腔念珠菌的侵袭性有一定的调节作用。白色念珠菌通过细胞壁重组。
Candida albicans is maintained as a commensal by immune mechanisms at the oral epithelia. Oral antifungal peptide Histatin 5 (Hst 5) may function in innate immunity, but the specific role Hst 5 plays in C. albicans commensalism is unclear. Since Zn-binding potentiates the candidacidal activity of Hst 5, we hypothesized that Hst 5+Zn would elicit a unique fungal stress response to shape interactions between C. albicans and oral epithelial cells (OECs). We found that Hst 5+Zn but not Hst 5 alone resulted in the activation of cell wall integrity (CWI) signaling, and deletion mutants were then used to determine that CWI-mediated chitin synthesis was protective against killing. Using flow cytometry, we confirmed that Hst 5+Zn-treated cells had significantly elevated levels of cell-wall chitin, mannan and β-1,3 glucan compared to Hst 5-treated cells. We then tested the activation of host signaling components involved in C. albicans cell-wall recognition. The immunoblot assay of C. albicans-exposed oral epithelial cells showed increased activation of EphA2 and NF-κB but not EGFR. Interestingly, C. albicans treated with Hst 5+Zn induced the global suppression of pro-inflammatory cytokine release from OECs, but an increase in negative regulator IL-10. Hst 5+Zn-treated cells were more adherent but ultimately less invasive to OECs than control cells, thus indicating lowered virulence. Therefore, Hst 5+Zn-treated C. albicans cells are discerned by epithelial monolayers, but are less virulent and promote anti-inflammatory signaling, suggesting that Hst 5+Zn in combination could play a role in regulating commensalism of oral C. albicans through cell wall reorganization.
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