Background: Attenuated NYVAC and MVA poxvirus strains are currently used for vaccine development against a broad spectrum of diseases. Whilst these vectors have been shown to be immunogenic and safe in humans, the innate immune responses they elicit remain largely unknown.
Aim: To assess the response of human THP-1 cells and mouse dendritic cells to poxviruses infection and to elucidate the role of the Toll-like-receptor (TLR) pathways in that response.
Results: MVA-stimulated THP-1 monocytes secreted large amounts of chemokines (MIP-1, MCP-1, IP-10, RANTES), but low levels of proinflammatory cytokines (TNF, IL-6, IL-1beta). In contrast, NYVAC induced weak production of both cytokines and chemokines in THP-1 cells. Using wild-type and TLR2, TLR4, MyD88 and TRIF deficient mouse dendritic cells, we observed that TLR2-MyD88 was essential for production of chemokines, but dispensable for IFNbeta production, after stimulation with MVA.
Conclusion: MVA triggers innate immune responses of macrophages and dendritic cells via TLR-dependent and TLR-independent pathways. Work is in progress to identify the TLR-independent pathway(s) activated by MVA.