Abstract
Many viruses have evolved complex mechanisms to avoid or block either the induction of, or the action of interferons. Interferons (IFNs) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. Plasmacytoid dendritic cells (pDCs) are specialised interferon producing cells and play a crucial role in the control of viral infections. Here we examine the interaction of plasmacytoid dendritic cells with two viruses -both of which are capable of blocking interferon in host cells. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active IFN. These cells represented less than 0.1% of the total lymphocyte population in blood, pseudoafferent lymph, and lymph nodes. Phenotypic analysis identified these cells as bovine pDCs (CD3-CD14- CD21-CD11c- NK-γδTCR-CD4+ MHCII+ CD45RB+ CD172a+ CD32+). High levels of type-I IFN were generated by these cells in vitro in response to Toll-like receptor 9 (TLR-9) agonist CpG and foot-and mouth disease virus (FMDV) immune complexes. In contrast, immune complexes with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type-I IFN response. Depletion of CD4 cells in vivo resulted in a significant reduction of serum type-I IFN serum early during FMDV infection compared to control animals. Bovine pDCs are also the main producers of IFN in response to Bovine Viral Diarrhoea Virus (BVDV) infection however the IFN produced was predominantly type-III IFN both in vivo and in vitro. In conclusion, pDCs interacting with immune-complexed virus are the major source of type-I IFN production during acute FMDV infection in cattle, very little type-III IFN is produced. Infection of pDCs with BVDV leads to the production of predominantly type-III IFN.