PMID- 26446939 OWN - NLM STAT- MEDLINE DCOM- 20160526 LR - 20181202 IS - 1873-2542 (Electronic) IS - 0378-1135 (Linking) VI - 180 IP - 3-4 DP - 2015 Nov 18 TI - 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. PG - 223-9 LID - S0378-1135(15)30032-8 [pii] LID - 10.1016/j.vetmic.2015.09.014 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Richmond, O AU - Richmond O AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. FAU - Cecere, T E AU - Cecere TE AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. Electronic address: tcecere@vt.edu. FAU - Erdogan, E AU - Erdogan E AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. FAU - Meng, X J AU - Meng XJ AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. FAU - Pineyro, P AU - Pineyro P AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. FAU - Subramaniam, S AU - Subramaniam S AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. FAU - Todd, S M AU - Todd SM AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. FAU - LeRoith, T AU - LeRoith T AD - Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States. LA - eng PT - Journal Article DEP - 20150921 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (B7-2 Antigen) RN - 0 (B7-H1 Antigen) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Apoptosis MH - B7-2 Antigen/*metabolism MH - B7-H1 Antigen/*metabolism MH - Cells, Cultured MH - Circoviridae Infections/*immunology MH - Circovirus MH - Coinfection/*immunology/virology MH - Dendritic Cells/*metabolism/virology MH - Interleukin-10/metabolism MH - Leukocytes/immunology MH - Porcine Reproductive and Respiratory Syndrome MH - Porcine respiratory and reproductive syndrome virus MH - Swine/immunology MH - Swine Diseases/virology MH - T-Lymphocytes, Regulatory/*immunology OTO - NOTNLM OT - Co-infection OT - Monocyte derived dendritic cells (MoDC) OT - Porcine circovirus associated disease (PCVAD) OT - Porcine circovirus type 2 (PCV2) OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Programed cell death-1 (PD-1) OT - Programed death ligand-1 (PD-L1) EDAT- 2015/10/09 06:00 MHDA- 2016/05/27 06:00 CRDT- 2015/10/09 06:00 PHST- 2015/04/20 00:00 [received] PHST- 2015/09/03 00:00 [revised] PHST- 2015/09/16 00:00 [accepted] PHST- 2015/10/09 06:00 [entrez] PHST- 2015/10/09 06:00 [pubmed] PHST- 2016/05/27 06:00 [medline] AID - S0378-1135(15)30032-8 [pii] AID - 10.1016/j.vetmic.2015.09.014 [doi] PST - ppublish SO - Vet Microbiol. 2015 Nov 18;180(3-4):223-9. doi: 10.1016/j.vetmic.2015.09.014. Epub 2015 Sep 21.