Papillomavirus virus‐like particles induce cytokines characteristic of innate immune responses in plasmacytoid dendritic cells

Abstract

Human papillomavirus (HPV) virus-like particles (VLP) are being extensively tested as vaccines for the prevention of HPV-associated cervical cancer. Dendritic cells (DC) acquire and present antigens, initiating innate and adaptive immune responses. It has been shown previously that DC of the myeloid lineage are capable of generating adaptive immune responses to HPV VLP in vitro. However, the capacity of plasmacytoid DC (pDC) to acquire HPV VLP and the nature of the immune response generated have not been reported. In this study we found that freshly isolated as well as CpG-matured pDC bind papillomavirus VLP and that internalization occurs preferentially in the immature pDC. In contrast to myeloid DC, pDC did not undergo phenotypic maturation upon exposure to HPV16 VLP. However, HPV16 VLP induced pDC to secrete of IFN-a and IL-6, both cytokines that play a role in the generation of antibody responses, as well as TNFa and IL-8. Given that VLP do not contain viral nucleic acids, these results indicate that viral capsids alone may be capable of inducing cytokine production by pDC. Finally, CpG-activated pDC, but not pDC exposed to HPV16 VLP, activated lymphocytes to secrete IL-10 and low levels of IFN-c. Together these findings suggest a possible immunogenic effect of pDC in the setting of VLP vaccination.

Baculovirus-Derived Human Immunodeficiency Virus Type 1 Virus-Like Particles Activate Dendritic Cells and Induce Ex Vivo T-Cell Responses

“…The apparent discordance of these results could be due to a different optimal timing for the sample collection and needs to be evaluated by more extensive observations. Nevertheless, the production of IFN-␥ by DCs induced with enveloped or nonenveloped VLP produced in different expression systems (prokaryotic, yeast, and baculovirus) is still a debated issue (18,28,30,49,53,54). In particular, Yang et al (53), reported that the CD8␣ ϩ…”

AS04, an Aluminum Salt- and TLR4 Agonist-Based Adjuvant System, Induces a Transient Localized Innate Immune Response Leading to Enhanced Adaptive Immunity

“…HPV L1 VLPs have been reported elsewhere to induce cytokine response in DCs, monocytes, and macrophages (41)(42)(43), possibly in a TLR-dependent fashion (44,45). Abs against HPV L1 VLPs were found to be reduced in TLR4-deficient mice by Yang et al (44) but not by others (46).…”

Disturbed Patterns of Immunocompetent Cells in Usual-Type Vulvar Intraepithelial Neoplasia

“…The results are also in agreement with the suspected role of pDCs in viral infections. Lenz and colleagues (21) showed in an in vitro study that HPV-16 is bound by freshly isolated immature pDCs and CpG maturated pDCs, that internalization of the virus preferentially occurs in immature pDCs, and that it induces the production of IFN-a and IL-6, important factors for the production of antibodies. Bontkes and colleagues (22) showed that pDCs are present in cervical cancer lesions and that HPV-16 virus-like particles are able to activate pDCs.…”