Papillomavirus-like particles induce acute activation of dendritic cells

The role of viral structural proteins in the initiation of adaptive immune responses is poorly understood. To address this issue, we focused on the ef fect of noninfectious papillomavirus-like particles (VLPs) on dendritic cel l (DC) activation. We found that murine bone marrow-derived dendritic cells (BMDCs) effectively bound and rapidly internalized bovine papillomavirus V LPs. Exposure to fully assembled VLPs of bovine papillomavirus, human papil lomavirus (HPV)16 or HPV18, but not to predominately disordered HPV16 capso mers, induced acute phenotypic maturation of BMDCs. Structurally similar po lyomavirus VLPs bound to the DC surface and were internalized, but failed t o induce maturation. DCs that had incorporated HPV16 VLPs produced proinfla mmatory cytokines IL-6 and TNF-alpha however, the release of these cytokine s was delayed relative to LPS activation. Production of IL-12p70 by VLP-exp osed DCs required the addition of syngeneic T cells or rIFN-gamma. Finally, BMDCs pulsed with HPV16 VLPs induced Th1-dominated primary T cell response s in vitro. Our data provide evidence that DCs respond to intact papillomav iruis capsids and that they play a central role in VLP-induced immunity. Th ese results offer a mechanistic explanation for the striking ability of pap illomavirus VLP-based vaccines to induce potent T and B cell responses even in the absence of adjuvant.