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

•PD-L1 expression is increased in dendritic cells following PCV2/ PRRSV co-infection.•CD86 expression is decreased in dendritic cells following PCV2/PRRSV co-infection.•IL-10 expression is increased in dendritic cells following PCV2 /PRRSV co-infection.•The PD-L1/PD-1 axis causes apoptosis, anergy, and the induction of regulatory T-cells.•This data provides potential mechanisms in PCVAD pathogenesis. 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+CD25HIGHFoxP3+ 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.