Horváth Márton, Nagy Gábor, Zsindely Nóra, Bodai László, Horváth Péter, Vágvölgyi Csaba, Nosanchuk Joshua D, Tóth Renáta, Gácser Attila
Department of Microbiology, University of Szeged, Szeged, Hungary.
Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
mSystems. 2021 May 11;6(3):e00163-21. doi: 10.1128/mSystems.00163-21.
Oral epithelial cells monitor microbiome composition and initiate immune response upon dysbiosis, as in the case of imbalances. species, such as and , are the most prevalent yeasts in the oral cavity. Comparison of healthy oral epithelial cell responses revealed that while infection robustly activated inflammation cascades, primarily activated various inflammation-independent pathways. In posttranscriptional regulatory processes, several miRNAs were altered by both species. For , the dose of yeast cells directly correlated with changes in transcriptomic responses with higher fungal burdens inducing significantly different and broader changes. MicroRNAs (miRNAs) associated with carbohydrate metabolism-, hypoxia-, and vascular development-related responses dominated with infection, whereas altered miRNAs linked to inflammatory responses. Subsequent analyses of hypoxia-inducible factor 1α (HIF1-α) and hepatic stellate cell (HSC) activation pathways predicted target genes through which miRNA-dependent regulation of yeast-specific functions may occur, which also supported the observed species-specific responses. Our findings suggest that is recognized as a commensal at low doses by the oral epithelium; however, increased fungal burden activates different pathways, some of which overlap with the inflammatory processes robustly induced by A relatively new topic within the field of immunology involves the role of miRNAs in innate as well as adaptive immune response regulation. In recent years, posttranscriptional regulation of host-pathogenic fungal interactions through miRNAs was also suggested. Our study reveals that the distinct nature of human oral epithelial cell responses toward and is possibly due to species-specific fine-tuning of host miRNA regulatory processes. The findings of this study also shed new light on the nature of early host cell transcriptional responses to the presence of and highlight the species' potential inflammation-independent host activation processes. These findings contribute to our better understanding of how miRNA deregulation at the oral immunological barrier, in noncanonical immune cells, may discriminate between fungal species, particularly species with high or low pathogenic potential.
口腔上皮细胞监测微生物群组成，并在生态失调（如失衡情况）时引发免疫反应。白色念珠菌和光滑念珠菌等物种是口腔中最常见的酵母。健康口腔上皮细胞反应的比较显示，虽然白色念珠菌感染强烈激活炎症级联反应，但光滑念珠菌主要激活各种与炎症无关的途径。在转录后调控过程中，两种物种都改变了几种微小RNA（miRNA）。对于白色念珠菌，酵母细胞的剂量与转录组反应的变化直接相关，真菌负荷越高，诱导的差异越显著且变化范围越广。与碳水化合物代谢、缺氧和血管发育相关反应相关的微小RNA（miRNA）在白色念珠菌感染中占主导地位，而光滑念珠菌改变了与炎症反应相关的miRNA。随后对缺氧诱导因子1α（HIF1-α）和肝星状细胞（HSC）激活途径的分析预测了可能发生miRNA依赖性酵母特异性功能调节的靶基因，这也支持了观察到的物种特异性反应。我们的研究结果表明，口腔上皮细胞在低剂量时将光滑念珠菌识别为共生菌；然而，真菌负荷增加会激活不同的途径，其中一些途径与白色念珠菌强烈诱导的炎症过程重叠。免疫学领域中一个相对较新的主题涉及miRNA在先天免疫和适应性免疫反应调节中的作用。近年来，也有人提出通过miRNA对宿主-致病性真菌相互作用进行转录后调控。我们的研究表明，人类口腔上皮细胞对白色念珠菌和光滑念珠菌反应的不同性质可能是由于宿主miRNA调控过程的物种特异性微调。这项研究的结果也为宿主细胞对白色念珠菌和光滑念珠菌存在的早期转录反应的性质提供了新的线索，并突出了这些物种潜在的与炎症无关的宿主激活过程。这些发现有助于我们更好地理解在口腔免疫屏障中，非经典免疫细胞中miRNA失调如何区分真菌物种，特别是具有高或低致病潜力的念珠菌物种。
