- INTRODUCTION
- MATERIALS AND METHODS
- Viruses and vaccines.
- Culture medium and reagents.
- Human DCs.
- Infection of human DCs with CYD1–4.
- Extraction of RNA, reverse transcription, and real-time polymerase chain reaction (RT-PCR).
- Antibodies for surface and intracellular immunostaining.
- Immunostaining and flow cytometry analysis.
- Cytokine production in culture supernatants.
- Statistical analysis.
- RESULTS
- DISCUSSION
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INNATE IMMUNE RESPONSES IN HUMAN DENDRITIC CELLS UPON INFECTION BY CHIMERIC YELLOW-FEVER DENGUE VACCINE SEROTYPES 1–4
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-α (TNF-α), but no IL-10, IL-12, or IL-1α. Parental dengue viruses induced a similar array of cytokines, but more TNF-α, 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.