Global Gene Expression Profiling of Myeloid Immune Cell Subsets in Response to In Vitro Challenge with Porcine Circovirus 2b

PLoS One

Mick Watson¹  Sylvia Grierson²  Falko Steinbach²  Bettina Mavrommatis³  Robert Patterson³  Dirk Werling³  Victoria Offord³  Theo Kanellos⁴ 

[1] ARK-Genomics, The Roslin Institute & R(D)SVS, University of Edinburgh, Midlothian, Edinburgh, United Kingdom;Department of Virology, Animal Health and Veterinary Laboratories Agency, Addlestone, United Kingdom;The Royal Veterinary College, Hatfield, United Kingdom;Zoetis Animal Health, Paris, France

关键词: Gene expression;    Immune cells;    Immune response;    Swine;    Cytokines;    Apoptosis;    Microarrays;    Viral gene expression;   

DOI  :  10.1371/journal.pone.0091081

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY