Vitamin D Regulates the Expression of Immune and Stress Response Genes in Dengue Virus-infected Macrophages by Inducing Specific MicroRNAs

Title:Vitamin D Regulates the Expression of Immune and Stress Response Genes in Dengue Virus-infected Macrophages by Inducing Specific MicroRNAs

Volume: 10 Issue: 4

Author(s): Geysson Javier Fernandez, Jorge Andrés Castillo, Diana Marcela Giraldo and Silvio Urcuqui-Inchima*

Affiliation:

• Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín,Colombia

Keywords: microRNAs, Vitamin D, immunomodulation, inflammation, cellular stress, macrophages, pathogenesis.

Abstract: Background: The pathogenesis associated with Dengue virus (DENV) infection is marked by the impairment of host immune response. Consequently, the modulation of immune response has emerged as an important therapeutic target for the control of DENV infection. Vitamin D has been shown to regulate the immune response in DENV infection, although the molecular mechanism remains poorly understood. Post-transcriptional regulation of mRNA by miRNAs offers an opportunity to gain insight into the immunomodulation mediated by vitamin D.

Objective: Previously, it has been observed that a high dose of vitamin D (4000 IU) decreased DENV-2 infection and inflammatory response in monocyte-derived macrophages (MDMs). Here, we examine whether high or low doses of vitamin D supplements exert differential effect on miRNA expression in DENV-infected macrophages.

Methods: We analyzed miRNA expression profiles in MDMs isolated from healthy individuals who were given either 1000 or 4000 IU/day of vitamin D for 10 days. MDMs before or after vitamin D supplementation were challenged with DENV-2, and miRNAs profiles were analyzed by qPCR arrays.

Results: DENV-2 infected MDMs supplemented with 4000 IU, showed up-regulation of miR-374a-5p, miR-363-3p, miR-101-3p, miR-9-5p, miR-34a-5p, miR-200a-3p, and the family of miRNAs miR-21-5p, and miR-590-p. The miRNA profile and predicted target mRNAs suggested regulatory pathways in MDMs obtained from healthy donors who received higher doses of vitamin D. These DENV-2 infected MDMs expressed a unique set of miRNAs that target immune and cellular stress response genes.

Conclusion: The results suggest vitamin D dose-dependent differential expression of miRNAs target key signaling pathways of the pathogenesis of dengue disease.

Cite this article as:

Fernandez Javier Geysson , Castillo Andrés Jorge , Giraldo Marcela Diana and Urcuqui-Inchima Silvio *, Vitamin D Regulates the Expression of Immune and Stress Response Genes in Dengue Virus-infected Macrophages by Inducing Specific MicroRNAs, MicroRNA 2021; 10 (4) . https://dx.doi.org/10.2174/2211536610666211221151949