High-dose of vitamin D supplement is associated with reduced susceptibility of monocyte-derived macrophages to dengue virus infection and pro inflammatory cytokine production: An exploratory study

Background. Dengue, one the most important public health problems in tropical and subtropical areas, is the most important mosquito-borne viral infection in humans. In the absence of effective treatment and vaccine against dengue, the active form of vitamin D could play a central role in protection against dengue virus (DENV), the causal agent of dengue. Recently we reported that monocyte-derived macrophages (MDMs) differentiated in the presence of vitamin D, in addition to expressing lower levels of mannose receptor, are less susceptible to DENV infection and produce low levels of pro-inflammatory cytokines, compared to MDMs differentiated in the absence of vitamin D. Objective: The aim of this study was to determine that oral vitamin D supplementation exerts an effect on DENV susceptibility and pro-inflammatory cytokine production in MDMs. Methods: Healthy individuals were supplemented with 1000 or 4000 international units (IU)/day of vitamin D during 10 days. Before and after vitamin D supplementation, a peripheral blood (PB) sample was taken and the monocytes recovered were used to obtain MDMs and were challenged with DENV-2. Furthermore, the expression of genes encoding vitamin D receptor (VDR), CYP24A1 and CAMP were analyzed using real-time quantitative PCR. Results: The data indicate that macrophages differentiated from monocytes obtained from healthy donors who received higher doses of vitamin D (4000 IU/day), exhibited higher resistance to DENV-2 infection and produced a significant decrease of pro-inflammatory cytokines and high production of interleukin-10 (IL-10). Furthermore, a significant decrease in intracellular toll-like receptor (TLR) and CAMP mRNA was observed. Conclusion: A supplement of 4000 IU/day of vitamin D may represent an adequate dose to control dengue progression and DENV replication. Although the results of our study suggest that the vitamin D status can influence the immune response, further studies are needed to determine the feasibility of vitamin D as anti-DENV agent and immune modulator.