Impairment of CD4+ T Cell Polarization by Dengue Virus–Infected Dendritic Cells

BACKGROUND: The production of type I interferon alpha/beta (IFN-α/β) is crucial to viral clearance during dengue virus (DENV) infection; however, in vitro-infected dendritic cells (DCs) exhibit a decreased capacity to respond to IFN-α/β stimulation, and antigen-presenting cells (APCs) isolated from patients with acute DENV infection exhibit defects in T cell priming. METHODS: In order to ascertain the stimulatory capacity of primary human monocyte-derived DCs infected with wild-type DENV isolates, representing a range of genotypes and disease outcomes, we cocultured infected DCs with allogeneic-naive CD4(+) T cells. The gene expression patterns of IFN-α/β sensitive genes were quantitated to determine if the infected DCs displayed a blunted IFN-α/β response. RESULTS: DENV-infected DCs induced the initial proliferation of naive CD4(+) T cells but they remained nonpolarized in effector function. The expression of IFN-α/β-stimulated genes was downregulated, revealing that the inhibition of IFN-α/β signaling is conserved among endemic DENV serotype 2 strains. CONCLUSIONS: The failure of naive CD4(+) T cells to differentiate into IFN gamma-producing effector T cells when primed by DENV-infected DCs cannot be explained solely by a block in IFN-α/β signaling, suggesting that the ability of DENV to evade the early host response is multifaceted.