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

Abstract

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.

Keywords: Inflammatory cytokines; Innate immunity; Interferon; Porcine reproductive and respiratory syndrome virus; Quil A.