title: Global gene expression profiling of myeloid immune cell subsets in response to in vitro challenge with porcine circovirus 2b.
abstract: Compelling evidence suggests that the early interaction between porcine circovirus 2 (PCV-2) and the innate immune system is the key event in the pathogenesis of Post-Weaning Multisystemic Wasting Syndrome (PMWS). Furthermore, PCV2 has been detected in bone-marrow samples, potentially enabling an easy spread and reservoir for the virus. To assess the gene-expression differences induced by an in-vitro PCV2b infection in different three different myeloid innate immune cell subsets generated from the same animal, we used the Agilent Porcine Gene Expression Microarray (V2). Alveolar macrophages (AMØs), monocyte-derived dendritic cells (MoDCs) and bone-marrow cells (BMCs) were generated from each animal, and challenged with a UK-isolate of a PCV2 genotype b-strain at a MOI of 0.5. Remarkably, analysis showed a highly distinct and cell-type dependent response to PCV2b challenge. Overall, MoDCs showed the most marked response to PCV2b challenge in vitro and revealed a key role for TNF in the interaction with PCV2b, whereas only few genes were affected in BMCs and AMØs. These observations were further supported by an enrichment of genes in the downstream NF-κB Signalling pathway as well as an up regulation of genes with pro-apoptotic functions post-challenge. PCV2b challenge increases the expression of a large number of immune-related and pro-apoptotic genes mainly in MoDC, which possibly explain the increased inflammation, granulomatous inflammation and lymphocyte depletion seen in PMWS-affected pigs.
authors.affiliation: The Royal Veterinary College, Hatfield, United Kingdom.
authors.forename: Bettina
authors.initials: B
authors.lastname: Mavrommatis
authors.affiliation: The Royal Veterinary College, Hatfield, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Offord
authors.affiliation: The Royal Veterinary College, Hatfield, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Patterson
authors.affiliation: ARK-Genomics, The Roslin Institute & R(D)SVS, University of Edinburgh, Midlothian, Edinburgh, United Kingdom.
authors.forename: Mick
authors.initials: M
authors.lastname: Watson
authors.affiliation: Zoetis Animal Health, Paris, France.
authors.forename: Theo
authors.initials: T
authors.lastname: Kanellos
authors.affiliation: Department of Virology, Animal Health and Veterinary Laboratories Agency, Addlestone, United Kingdom.
authors.forename: Falko
authors.initials: F
authors.lastname: Steinbach
authors.affiliation: Department of Virology, Animal Health and Veterinary Laboratories Agency, Addlestone, United Kingdom.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Grierson
authors.affiliation: The Royal Veterinary College, Hatfield, United Kingdom.
authors.forename: Dirk
authors.initials: D
authors.lastname: Werling
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018173:Circoviridae Infections / Q000662:veterinary*; D017925:Circovirus / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000821:virology; D058977:Molecular Sequence Annotation; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D059467:Transcriptome