Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.

Abstract

Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.