Infection of human dendritic cells by Dengue virus causes cell maturation and cytokine production

Dengue virus (DV) infection is a major problem in public health. It can cau se fatal diseases such as Dengue hemorrhagic fever and Dengue shock syndrom e. Dendritic cells (DC) are professional APCs required for establishing a p rimary immune response. Here, we investigated the role of human PBMC-derive d DC in DV infection. Using different techniques, including plaque assay, f low cytometry analysis, nested RT-PCR, and confocal microscope and electron microscope examinations, we show that DV can enter cultured human DC and p roduce virus particles. After entrance, DV could be visualized in cystic ve sicles, vacuoles, and the endoplasmic reticulum, The DV-infected DC also sh owed proliferation and hypertrophy of the endoplasmic reticulum as well as the swollen mitochondria. In addition, the DV-stimulated DC could express m aturation markers such as B7-1, B7-2, HLA-DR, CD11b, and CD83. Furthermore, the infection of DC by DV induced production of TNF-alpha and IFN-alpha, b ut not IL-6 and IL-12. Although DC underwent spontaneous apoptosis in the a bsence of feeding cytokines, this process appeared to be delayed after DV i nfection. Our observations provide important information in understanding t he pathogenesis of DV infection.