Respiratory Syncytial Virus Infection Reduces Kynurenic Acid Production and Reverses Th17/Treg Balance by Modulating Indoleamine 2,3-Dioxygenase (IDO) Molecules in Plasmacytoid Dendritic Cells

BACKGROUND: Respiratory syncytial virus (RSV) infection causes a world-wide medical and economic burden. This study analyzed the effects of RSV infection on plasmacytoid dendritic cells (pDCs) and evaluated the immunopathogenesis of RSV infection by measuring relative numbers of FoxP3+ Treg cells and Th17 cells. MATERIAL/METHODS: pDCs were isolated from human blood samples, purified using magnetic microbeads, and treated with RSV, IFN-γ, or vehicle. These cells were mixed with purified CD4+ T cells to yield preparations of pDCs+T cells+vehicle, pDCs+T cells+RSV, and pDCs+T cells+IFN-γ. Preparations of pDCs+T cells+RSV were also incubated with an inducer or an inhibitor of indoleamine 2,3-dioxygenase (IDO). Kynurenic acid concentration was measured by high-pressure liquid chromatography (HPLC). The differentiation of Foxp3+ Treg and Th17 cells from CD4+ T cells was determined by flow cytometry. RESULTS: pDCs were successfully isolated and purified using the magnetic microbeads. Compared with preparations of pDCs+T cells+vehicle, RSV infection (pDCs+T cells+RSV) significantly reduced and IFN-γ treatment (pDC+T cells+IFN-γ) increased kynurenic acid concentrations and the proportions of Foxp3(+) Tregs (p<0.05 each). Conversely, RSV infection increased and IFN-γ treatment decreased the proportions of Th17 cells (p<0.05 each). RSV infection reduced kynurenic acid concentrations and inhibited the transformation from Th17 to Foxp3(+) Tregs by modulating IDO molecules. CONCLUSIONS: RSV infection reduced the production of kynurenic acid and inhibited transformation from Th17 to Foxp3(+) Tregs (Th17/Treg balance) by modulating IDO molecules in pDCs.