Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.
Sci Rep. 2017 Jan 17;7:40599. doi: 10.1038/srep40599.
Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment.
维生素 A 和维生素 D 是两种必需的营养物质，在人类中具有广泛的多效性。除了它们在细胞分化、胚胎发生、组织维持和骨骼/钙稳态方面的作用外，这两种维生素由于与免疫特性有关而引起了相当大的关注。然而，我们对它们在感染期间的免疫调节潜力的了解仅限于以单个基因为中心的研究，这些研究不能反映免疫过程的复杂性。在本研究中，我们采用了基于 RNA 测序的综合方法来确定维生素 A 和 D 在感染期间的整体免疫调节作用。使用人类单核细胞作为宿主细胞，我们研究了两种维生素在感染三种不同病原体（烟曲霉、白色念珠菌和大肠杆菌）时的差异作用。两种维生素都表现出了出人意料的对抗病原体诱导的转录反应的能力。感染后，我们分别鉴定出了 346 个和 176 个与免疫相关的基因，它们分别受到 atRA 和 vitD 的调节。这种免疫调节活性依赖于炎症刺激，使我们能够区分每种刺激环境特有的调节模式。此外，我们还探索了维生素介导的免疫反应调节的可能直接和间接机制。我们的研究结果强调了在危重病患者中监测维生素的重要性。此外，我们的结果为 atRA 和 vitD 作为抗炎治疗的治疗选择提供了依据。
