Muhammad Syed Aun, Fatima Nighat, Syed Nawazish-I-Husain, Wu Xiaogang, Yang X Frank, Chen Jake Y
Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University (BZU), Multan, Pakistan.
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan.
PLoS One. 2015 Aug 27;10(8):e0136454. doi: 10.1371/journal.pone.0136454. eCollection 2015.
Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans). Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format) was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions following invasive Candidal infection. These findings contribute to our understanding of host cell response to Candidal systemic infections.
侵袭性念珠菌病是由白色念珠菌引起的具有潜在生命威胁的系统性真菌感染。念珠菌进入血流并扩散至全身，在住院患者、免疫功能低下者或患有慢性疾病的人群中较为常见。这种感染具有机会性，风险始于白色念珠菌在黏膜皮肤表面和呼吸道上皮的定植。微小RNA（miRNA）是小的非编码RNA，几乎参与调控每个细胞过程。它们调节和控制mRNA稳定性水平以及转录后基因表达。miRNA的异常表达与许多疾病状态相关，基于miRNA的疗法正在研发中。在本研究中，我们调查了侵袭性念珠菌感染的呼吸道上皮细胞中miRNA表达谱的可能变化。为此，在治疗前获取了医院实验室中感染个体的呼吸道上皮组织。通过从同一感染个体的血培养物中分离出白色念珠菌来确诊侵袭性念珠菌感染。使用他汀抗体（S - 44）通过流式细胞仪（FACSCalibur细胞仪；德国海德堡BD生物科学公司）评估上皮组织的纯度。采用TaqMan定量实时PCR（TaqMan低密度阵列形式）进行miRNA表达谱分析。所研究的miRNA中，55种miRNA的表达水平在感染组织中显著改变。与对照相比，一些miRNA表现出显著增加（miR - 16 - 1）或表达降低（miR - 17 - 3p）。对这些miRNA靶向基因的基因本体富集分析表明念珠菌感染影响许多重要的生物学途径。总之，miRNA表达水平的紊乱表明侵袭性念珠菌感染后病理过程级联反应的变化以及呼吸道上皮功能的调节。这些发现有助于我们理解宿主细胞对念珠菌系统性感染的反应。
