title: Bovine plasmacytoid dendritic cells are the major source of type I interferon in response to foot-and-mouth disease virus in vitro and in vivo.
abstract: Type I interferons (alpha/beta interferons [IFN-α/β]) 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) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type I IFN signal transduction pathway. Using density gradient separation and cell sorting, we have highly enriched a population of bovine cells capable of producing high levels of biologically active type I 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(-) TCRδ(-) CD4(+) MHC II(+) 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 formed with UV-inactivated FMDV or FMDV empty capsids failed to elicit a type I IFN response. Depletion of CD4 cells in vivo resulted in levels of type I IFN in serum early during FMDV infection that were significantly lower than those for control animals. In conclusion, pDCs interacting with immune-complexed virus are the major source of type I interferon production during acute FMDV infection in cattle.
authors.affiliation: The Institute for Animal Health, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Reid
authors.forename: Nicholas
authors.initials: N
authors.lastname: Juleff
authors.forename: Simon
authors.initials: S
authors.lastname: Gubbins
authors.forename: Helen
authors.initials: H
authors.lastname: Prentice
authors.forename: Julian
authors.initials: J
authors.lastname: Seago
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology*; D002499:Centrifugation, Density Gradient; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D005434:Flow Cytometry; D005536:Foot-and-Mouth Disease / Q000276:immunology*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D007370:Interferon Type I