Innate immune responses in human dendritic cells upon infection by chimeric yellow-fever dengue vaccine serotypes 1-4

Am J Trop Med Hyg. 2007 Jan;76(1):144-54.

Abstract

Dengue infection is an important public health issue worldwide. The ChimeriVax-Dengue (CYD) vaccine uses yellow fever (YF) 17D vaccine as a live vector. Dendritic cells (DCs) play a key role in initiating immune responses and could be an important primary target of dengue infection. We investigated in vitro the consequences of CYD infection of DCs on their activation/maturation and cytokine production. In CYD-infected DCs, we observed an up-regulation of HLA-DR, CD80, CD86, and CD83. Cells exposed to CYD secreted type I interferons, monocyte chemoattractant protein 1 (MCP-1)/CC chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), and low amounts of tumor necrosis factor-alpha (TNF-alpha), but no IL-10, IL-12, or IL-1alpha. Parental dengue viruses induced a similar array of cytokines, but more TNF-alpha, less IL-6, and less MCP-1/CCL-2 than induced by CYD. Chimeras thus induced DCs maturation and a controlled response accompanied by limited inflammatory cytokine production and consistent expression of anti-viral interferons, in agreement with clinical observations of safety and immunogenicity.

MeSH terms

  • Cell Adhesion Molecules / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology*
  • Dengue / immunology*
  • Dengue Vaccines / adverse effects
  • Dengue Vaccines / immunology*
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate / immunology*
  • Lectins, C-Type / metabolism
  • Receptors, Cell Surface / metabolism
  • Yellow Fever / immunology*
  • Yellow Fever Vaccine / immunology*

Substances

  • Cell Adhesion Molecules
  • Cytokines
  • DC-specific ICAM-3 grabbing nonintegrin
  • Dengue Vaccines
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Yellow Fever Vaccine