Selective dysfunction of subsets of peripheral blood mononuclear cells during pediatric dengue and its relationship with clinical outcome

During dengue virus (DENV) infection, a blockage of secretion of cytokines such as tumor necrosis factor (TNF)-α and members of the interferon (IFN) family has been described in vitro. We evaluated the functionality of monocytes as well as dendritic, B and T cells isolated from children with mild and severe dengue. Compared with those of healthy children, stimulated monocytes, CD4⁺ T cells and dendritic cells from children with dengue had lower production of proinflammatory cytokines. The interferon axis was dramatically modulated by infection as plasmacytoid dendritic cells (pDCs) and CD4⁺ T cells had low production of IFN-α and IFN-γ, respectively; plasma levels of IFN-α and IFN-γ were lower in severely ill children, suggesting a protective role. Patients with antigenemia had the highest levels of IFN-α in plasma but the lowest frequency of IFN-α-producing pDCs, suggesting that DENV infection stimulates a systemic type I IFN response but affects the pDCs function.