PMID- 24618842 OWN - NLM STAT- MEDLINE DCOM- 20150529 LR - 20220129 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 3 DP - 2014 TI - Global gene expression profiling of myeloid immune cell subsets in response to in vitro challenge with porcine circovirus 2b. PG - e91081 LID - 10.1371/journal.pone.0091081 [doi] LID - e91081 AB - 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 (AMOs), 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 AMOs. These observations were further supported by an enrichment of genes in the downstream NF-kappaB 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. FAU - Mavrommatis, Bettina AU - Mavrommatis B AD - The Royal Veterinary College, Hatfield, United Kingdom. FAU - Offord, Victoria AU - Offord V AD - The Royal Veterinary College, Hatfield, United Kingdom. FAU - Patterson, Robert AU - Patterson R AD - The Royal Veterinary College, Hatfield, United Kingdom. FAU - Watson, Mick AU - Watson M AD - ARK-Genomics, The Roslin Institute & R(D)SVS, University of Edinburgh, Midlothian, Edinburgh, United Kingdom. FAU - Kanellos, Theo AU - Kanellos T AD - Zoetis Animal Health, Paris, France. FAU - Steinbach, Falko AU - Steinbach F AD - Department of Virology, Animal Health and Veterinary Laboratories Agency, Addlestone, United Kingdom. FAU - Grierson, Sylvia AU - Grierson S AD - Department of Virology, Animal Health and Veterinary Laboratories Agency, Addlestone, United Kingdom. FAU - Werling, Dirk AU - Werling D AD - The Royal Veterinary College, Hatfield, United Kingdom. LA - eng GR - BB/E018394/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBS/E/D/20211552/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/FO18394/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140311 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Animals MH - Apoptosis/genetics/immunology MH - Bone Marrow Cells/immunology/metabolism/virology MH - Circoviridae Infections/*veterinary MH - Circovirus/*immunology MH - Dendritic Cells/immunology/metabolism/virology MH - *Gene Expression Profiling MH - Gene Expression Regulation MH - Macrophages, Alveolar/immunology/metabolism/virology MH - Molecular Sequence Annotation MH - Myeloid Cells/*immunology/*metabolism/virology MH - Signal Transduction MH - Swine MH - Swine Diseases/*genetics/*immunology/virology MH - Time Factors MH - Transcriptome PMC - PMC3949749 COIS- Competing Interests: Theo Kanellos is an employee of Zoetis Animal Health, Paris, whose company provided funding towards this study. Biobest Laboratories also provided funding for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2014/03/13 06:00 MHDA- 2015/05/30 06:00 PMCR- 2014/03/11 CRDT- 2014/03/13 06:00 PHST- 2013/10/28 00:00 [received] PHST- 2014/02/07 00:00 [accepted] PHST- 2014/03/13 06:00 [entrez] PHST- 2014/03/13 06:00 [pubmed] PHST- 2015/05/30 06:00 [medline] PHST- 2014/03/11 00:00 [pmc-release] AID - PONE-D-13-44339 [pii] AID - 10.1371/journal.pone.0091081 [doi] PST - epublish SO - PLoS One. 2014 Mar 11;9(3):e91081. doi: 10.1371/journal.pone.0091081. eCollection 2014.