Modulations of phenotype and cytokine expression of porcine bone marrow-derived dendritic cells by porcine reproductive and respiratory syndrome virus.

Phenotypic and functional property changes of bone marrow-derived immature dendritic cells (BM-imDCs) after porcine reproductive and respiratory syndrome virus (PRRSV) infection have been detailed in a previous report. A down-regulated expression of MHC I molecules along with an up-regulated expression of CD80/86 were observed in BM-imDCs after the exposure to PRRSV. In this study, we further investigate the expression of surface phenotypes of BM-imDCs in relation to their infection status. Exposure of PRRSV to BM-imDCs resulted in a down-regulated expression of MHC I and an up-regulated expression of CD80/86 in infected cells, as demonstrated by significant alterations in both percentage of expressing cells and mean fluorescence intensity (MFI) in PRRSV-positive cells. A significant suppression in MFI of MHC I and an increase in percentage of cells expressing CD80/86 were observed in noninfected bystander cells. We also demonstrated that exposure of BM-imDCs to PRRSV resulted in a significantly increased secretion of IL-1, IL-6, IL-8, IL-10 and IFN-gamma but not IL-12 or TNF-alpha. In addition, the PRRSV infection modulates cytokine expressions of BM-imDCs through their response to microbial pathogen-associated molecular patterns. These results will prove helpful in clarification of the factors that mediate host defense against PRRSV, as well as the possible interaction mechanisms between PRRSV and other microbes in the pathogenesis of PRRSV infection in pigs.

Expression of Toll-like receptor mRNA and cytokines in pigs infected with porcine reproductive and respiratory syndrome virus.

Field observations have suggested that porcine reproductive and respiratory syndrome virus (PRRSV) predispose pigs to secondary infections. The interaction between PRRSV and the secondary invaders has not yet been well elucidated. In this study, we investigated the mRNA expression of Toll-like receptors (TLR) in lymphoid organs and cells, and cytokine secretions by alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs) in response to pathogen-associated molecular patterns (PAMPs) in PRRSV-challenged pigs. TLR mRNA expressions were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and cytokine concentrations were determined using commercially available ELISA kits. PRRSV infection led to significantly increased secretions of IL-1beta and IL-6 by AMs of PRRSV-infected pigs. Infection of pigs with PRRSV also resulted in an increased secretion of IL-1beta by AMs in response to lipoteichoic acid (LTA) stimulation, and IL-6 by PBMCs in response to lipopolysaccharide (LPS) and LTA stimulation. Infection of pigs with PRRSV tended to up-regulate the mRNA expression of TLR2, 3, 4, 7 and 8 in at least one of the lymphoid tissues and cells. Further research is required to demonstrate the association between the enhanced expressions of the specific TLRs and the increased susceptibility to secondary agents with more severe clinical outcomes in PRRSV-infected pigs.

Phenotypic and functional modulation of bone marrow-derived dendritic cells by porcine reproductive and respiratory syndrome virus.

It is well documented that there is a delay in the development of effective immunity to porcine reproductive and respiratory syndrome virus (PRRSV) in infected and vaccinated pigs. This suggests that PRRSV might possess some inherent properties to evade host defense mechanisms during the early stage of infection. Dendritic cells (DCs) play a crucial role in the activation and control of T-cells in response to viral antigens. In this study, we investigated the phenotypic and functional property changes of bone marrow-derived immature DCs (BM-imDCs) that take place after infection by PRRSV. Results showed that BM-imDCs were permissive to PRRSV infection, as productive replication took place in these cells. A down-regulated expression of MHC I molecules along with an up-regulated expression of CD80/86 is observed at 48 h following infection. Also at 48h following PRRSV infection, a significant increase of IL-10 secretion by BM-imDCs was noticed. Results suggest that the inhibited expression of MHC I and the enhanced secretion of IL-10 by BM-imDCs after PRRSV infection might be among the strategies used by the virus to evade the host immune defenses.