Saponin Quil A up-regulates type I interferon-regulated gene and type I and II interferon expressions which are suppressed by porcine reproductive and respiratory syndrome virus

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses innate immune response following infection of myeloid antigen-presenting cells. Poor innate immune response results in weak and delayed PRRSV-specific adaptive immunity, and facilitates PRRSV replication, pathogenesis, and persistent infection. Numerous efforts have been made to enhance the effective innate and adaptive immune defenses to PRRSV, however, only a few attempts have so far elicited satisfactory results. The present study aims to evaluate in vitro the potential of saponin quil A to enhance the expression of type I interferon (IFN)-regulated gene, type I and II IFNs, and pro-inflammatory cytokines in PRRSV-inoculated peripheral blood mononuclear cells (PBMC). Naïve PBMC from four PRRSV-seronegative pigs were inoculated with PRRSV and subsequently stimulated with quil A in the absence or presence of either polyinosinic:polycytidylic acid (poly IC) or lipopolysaccharide (LPS). The mRNA expression levels of myxovirus resistance 1 (Mx1), interferon regulatory factor 3 (IRF3), IRF7, 2′-5′-oligoadenylatesynthetase 1 (OAS1), stimulator of interferon genes (STING), osteopontin (OPN), IFNα, IFNβ, IFNγ, interleukin-2 (IL-2), IL-10, IL-13, tumor necrosis factor alpha (TNFα), and transforming growth factor beta (TGFβ) were evaluated by real-time PCR. Compared with uninoculated PBMC, PRRSV significantly suppressed expression of all immune parameters except IL-2, IL-10, IL-13, and TGFβ. When compared with PRRSV-inoculated PBMC, stimulation with quil A significantly enhanced Mx1, IRF3, IRF7, OAS1, STING, IFNβ, and IFNγ mRNA expressions, and significantly reduced TGFβ mRNA expression. Our findings thus suggest that quil A has a potential to up-regulate the expression of type I IFN-regulated gene and type I and II IFNs which are suppressed by PRRSV. Therefore, it may serve as an effective immunostimulator for potentiating the innate immune defense to PRRSV.