title: The PD-L1/CD86 ratio is increased in dendritic cells co-infected with porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus, and the PD-L1/PD-1 axis is associated with anergy, apoptosis, and the induction of regulatory T-cells in porcine lymphocytes.
abstract: Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) continue to have a negative economic impact on global swine production operations. Host immune modulations that potentiate disease during PCV2 and/or PRRSV infections are important areas of ongoing research. In this study, we evaluated the expression levels of PD-L1, CD86, and IL-10 in order to phenotype dendritic cells following viral infection with PCV2b and/or PRRSV. The results showed that the inhibitory marker PD-L1 was significantly increased in monocyte derived dendritic cells (MoDC) in both singular PCV2 infection and PCV2/PRRSV co-infections. MoDC expression of stimulatory marker CD86 was significantly increased during singular PCV2 infections, while it was significantly decreased in the treatment groups co-infected with both PCV2 and PRRSV. IL-10 production was highest among MoDCs that were co-infected with PCV2 and PRRSV. These results indicate that dendritic cells develop a regulatory phenotype following PCV2/PRRSV co-infections. We further investigated the role of the PD-L1/PD-1 axis in lymphocyte anergy, apoptosis, and the induction of regulatory T-cells in porcine mononuclear cell populations. Lymphocyte populations with normal PD-1 expression had higher percentages of anergic, apoptotic lymphocytes and CD4(+)CD25(HIGH)FoxP3(+) regulatory T-cells when compared to a PD-1 deficient lymphocyte population. These results implicate the PD-L1/PD-1 axis in negative regulation of lymphocyte responses in pigs.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: O
authors.initials: O
authors.lastname: Richmond
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. Electronic address: tcecere@vt.edu.
authors.forename: T E
authors.initials: TE
authors.lastname: Cecere
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: E
authors.initials: E
authors.lastname: Erdogan
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: X J
authors.initials: XJ
authors.lastname: Meng
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: P
authors.initials: P
authors.lastname: Piñeyro
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: S
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: S M
authors.initials: SM
authors.lastname: Todd
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.
authors.forename: T
authors.initials: T
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D017209:Apoptosis; D051940:B7-2 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D018173:Circoviridae Infections / Q000276:immunology*; D017925:Circovirus; D060085:Coinfection / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D019318:Porcine Reproductive and Respiratory Syndrome; D019316:Porcine respiratory and reproductive syndrome virus; D013552:Swine / Q000276:immunology; D013553:Swine Diseases / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D016753:Interleukin-10
keywords: Co-infection; Monocyte derived dendritic cells (MoDC); Porcine circovirus associated disease (PCVAD); Porcine circovirus type 2 (PCV2); Porcine reproductive and respiratory syndrome virus (PRRSV); Programed cell death-1 (PD-1); Programed death ligand-1 (PD-L1)