To address this issue, the present study used immature human monocyte-derived DCs to assess the early events that occur after DCs encounter noninfectious EV71 VLPs and to investigate the ability of DCs to initiate primary T-cell responses. We found that EV71 VLPs trigger Tolllike receptor 4 and nuclear factor kappaB BMN673 signaling to induce phenotypic and functional maturation of DCs, which induces Th1-dominated immune responses. We believe that our findings might help to better elucidate the function of DCs in the pathogenesis of EV71 and the potential utility of VLPs for vaccination against EV71. Immunization with VLPs, which are empty particles that comprise viral capsid proteins alone, has been shown to protect against various infectious diseases. Given that immunogens containing viral nucleic acids may cause undesirable side effects, VLPs offer a safer alternative to intact viruses for clinic trials and routine vaccination programs. Studies of VLPs derived from important viruses, such as human immunodeficiency virus and Norwalk virus, have recently indicated that VLPs can induce the production of neutralizing Abs and cytotoxic Tlymphocyte responses. Moreover, VLPs of hepatitis B virus and human papillomavirus have been licensed for use as vaccines. In 2008, we found that EV71 VLPs prevent EV71 infection by increasing the titers of neutralizing Abs in mice. Recently, we also found that monkeys intramuscularly immunized with EV71 VLPs showed potent humoral and cellular immune responses to both EV71 VLPs and EV71 virions upon in vitro stimulation. Therefore, EV71 VLPs are a candidate vaccine for the prevention of EV71 infection. However, whether the immunized monkeys are protected from future infection remains to be investigated. Given that DCs are required for the initiation of a potent cellular immune response, the immunogenicity of vaccines may be dependent on the DC response. In this study, we investigated the interactions of EV71 VLPs with human DCs. We showed that EV71 VLPs bound to and activated DCs and identified TLR4 as a receptor for EV71 VLPs. Moreover, pulsing of human DCs with EV71 VLPs induced T-cell responses that were characterized by IFN-c secretion. This finding is similar to the results of our monkey study, in which the PBMCs from monkeys immunized with the EV71 VLP vaccine were stimulated with EV71 VLPs or inactivated EV71 as antigens; both groups of monkeys were able to induce T cell proliferation and higher levels of IFN-c secretion. Therefore, based on our current findings in human DCs in vitro, we speculated that DCs play an important role in presenting EV71 VLPs antigen to T cells, and may generate a memory immune response to EV71 in EV71 VLPs immunized monkeys. Many studies have focused on the application of human papillomavirus-like particles to DCs. The acute activation of DCs by human papillomavirus-like particles requires signaling events that involve TLR4 and NF-kB.