The ability of dendritic cells (DCs) to shape the adaptive immune response to viral infection is mediated largely by their maturation and activation state as determined by the surface expression of HLA molecules, costimulatory molecules, and cytokine production. Dengue is an emerging arboviral disease where the severity of illness is influenced by the adaptive immune response to the virus. In this report, we have demonstrated that dengue virus infects and replicates in immature human myeloid DCs. Exposure to live dengue virus led to maturation and activation of both the infected and surrounding, uninfected DCs and stimulated production of tumor necrosis factor alpha (TNF-␣) and alpha interferon (IFN-␣). Activation of the dengue virus-infected DCs was blunted compared to the surrounding, uninfected DCs, and dengue virus infection induced low-level release of interleukin-12 p70 (IL-12 p70), a key cytokine in the development of cell-mediated immunity (CMI). Dendritic cells (DCs) are bone marrow-derived cells that form a system of professional antigen-presenting cells and are an important component of the innate immune response. They are comprised of at least three distinct subpopulations, one in the lymphoid/plasmacytoid lineage and two in the myeloid lineage (1,20,26). Myeloid DCs are found in most nonlymphoid organs including the epidermis (Langerhans cells), dermis, gastrointestinal and respiratory mucosa, and the interstitia of vascular organs (37). Following the uptake and processing of antigen in the periphery, immature myeloid DCs differentiate to an activated/mature state and migrate to the T-cell-rich areas of lymphoid organs. Activated DCs are the unique stimulators of primary T-cell responses and potent stimulators of memory responses, and they produce an array of cytokines and chemokines (26,44,50,55). Thus, DCs are critical in the initiation of antimicrobial immunity, and they provide a crucial step in the development of adaptive immunity.Dengue is an emerging arboviral disease where the adaptive immune response plays a significant role in determining the severity of clinical illness. The dengue viruses are a group of four antigenically related mosquito-borne flaviviruses that produce a spectrum of clinical illness and significant morbidity throughout the tropics (30,35). Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) represent the most severe and potentially life-threatening manifestations of a dengue viral infection. DHF/DSS is characterized by the rapid onset of plasma leakage and coagulopathy near the time of defervescence and viremia resolution. The most significant risk factor for the development of DHF/DSS is acquisition of a second, heterotypic dengue virus infection (3,11,13). During this second dengue virus infection, it is postulated that the preexisting, cross-reactive, adaptive immune response leads to excessive cytokine production, complement activation, and the release of other phlogistic factors which produce DHF/DSS. Both the humoral and cellular components of adaptive ...