Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Parasitol Res. 2012 Sep;111(3):1093-101. doi: 10.1007/s00436-012-2937-3. Epub 2012 May 6.
Increasing evidence critically implicates miRNAs in the pathogenesis of diseases, but little is known in context with infectious diseases. This study investigates as to whether the testosterone-induced persistent susceptibility to blood-stage malaria of Plasmodium chabaudi coincides with changes in miRNA expression of the anti-malaria effectors sites spleen and liver. Female C57BL/6 mice were treated with vehicle or testosterone (T) for 3 weeks. Then, T treatment was discontinued for 12 weeks before challenge with 10(6) P. chabaudi-parasitized erythrocytes. The miRNA expression was examined after 12 weeks of T withdrawal and during infections at peak parasitemia on day 8 p.i. using miRXplore™ microarray technology. P. chabaudi infections induce an organ-specific response of miRNA expression. We can identify 25 miRNA species to be downregulated by more than 2-fold in the spleen and 169 miRNA species in the liver. Among these 194 miRNA species, there are 12 common miRNA species that are downregulated by 0.48-0.14-fold in both spleen and liver, which are miR-194, miR-192, miR-193A-3P, miR-145, miR-16, miR-99A, miR-99B, miR-15A, miR-152, let-7G, let-7B, and miR-455-3P. Only in the liver, there is an upregulation of the miR-142-5p by 2.5-fold and miR-342-3p by 5.1-fold. After 12 weeks of T withdrawal, the spleen exhibits only the miR-200A that is upregulated by 2.7-fold. In the liver, miR-376B, miR-493*, and miR-188-3P are upregulated by 2.4-fold, 2.2-fold, and 2.1-fold, respectively, and miR-347, miR-200A, and miR-200B are downregulated by approximately 0.4-fold. Upon infection, however, these changes are not sustained, i.e., the miRNA expressions of both spleen and liver of T-pretreated mice exhibit the same response to P. chabaudi malaria as that of vehicle-treated control mice. Our data suggest (1) that the P. chabaudi-induced downregulation of miRNA expression in spleen and liver is required to allow the upregulation of their numerous target genes in response to infection, and (2) that the T-induced persistent susceptibility to P. chabaudi does not affect the responsiveness of miRNA expression in spleen and liver to blood-stage malaria.
越来越多的证据表明 microRNA（miRNA）在疾病的发病机制中起着重要作用，但在传染病方面的了解还很少。本研究旨在探讨睾酮诱导的持续性对伯氏疟原虫血期疟的易感性是否与抗疟效应部位脾脏和肝脏的 miRNA 表达变化有关。雌性 C57BL/6 小鼠用载体或睾酮（T）处理 3 周。然后，在感染 10（6）感染伯氏疟原虫寄生虫的红细胞前，T 治疗停止 12 周。在 T 撤药后 12 周和感染高峰期（感染后第 8 天），使用 miRXplore™微阵列技术检查 miRNA 表达。伯氏疟原虫感染诱导 miRNA 表达的器官特异性反应。我们可以鉴定出 25 种在脾脏中下调超过 2 倍的 miRNA 物种和 169 种在肝脏中下调的 miRNA 物种。在这 194 种 miRNA 物种中，有 12 种常见的 miRNA 物种在脾脏和肝脏中均下调 0.48-0.14 倍，分别是 miR-194、miR-192、miR-193A-3P、miR-145、miR-16、miR-99A、miR-99B、miR-15A、miR-152、let-7G、let-7B 和 miR-455-3P。只有在肝脏中，miR-142-5p 上调 2.5 倍，miR-342-3p 上调 5.1 倍。T 撤药 12 周后，脾脏仅上调 miR-200A，上调 2.7 倍。在肝脏中，miR-376B、miR-493*和 miR-188-3P 分别上调 2.4 倍、2.2 倍和 2.1 倍，miR-347、miR-200A 和 miR-200B 下调约 0.4 倍。然而，在感染后，这些变化并没有持续，即 T 预处理小鼠的脾脏和肝脏的 miRNA 表达对伯氏疟原虫疟疾的反应与载体处理的对照小鼠相同。我们的数据表明：（1）伯氏疟原虫诱导的脾脏和肝脏中 miRNA 表达下调是允许其众多靶基因在感染时上调所必需的；（2）T 诱导的持续性对伯氏疟原虫的易感性并不影响脾脏和肝脏对血期疟原虫的 miRNA 表达的反应性。
