Program of Biotechnology, Faculty of Science, Maejo University, Chiang Mai 50290, Thailand.
Program of Biotechnology, Faculty of Science, Maejo University, Chiang Mai 50290, Thailand.
Vaccine. 2020 Apr 23;38(19):3570-3581. doi: 10.1016/j.vaccine.2020.03.019. Epub 2020 Mar 14.
This study evaluated the immunomodulatory effect of quercetin on improving cross protection of porcine reproductive and respiratory syndrome virus-1 (PRRSV-1) modified-live virus (MLV) vaccine against highly pathogenic (HP)-PRRSV-2 challenge. Ex vivo experiments demonstrated that quercetin significantly enhanced type I interferon-regulated genes (IRGs) and type I and II interferon (IFN), and significantly decreased pro- and anti-inflammatory cytokine expressions in HP-PRRSV-inoculated monocyte-derived macrophages. In vivo experiments divided pigs (4-week-old; n = 24) into four groups of six pigs. Group 1 and group 2 were immunized with PRRSV-1 MLV vaccine at 0 dpv (day post vaccination). Group 2 also received oral administration of quercetin at 0-49 dpv. Group 3 was injected with PRRSV-1 MLV vaccine solvent at 0 dpv. Group 4 served as strict control. Group 1-3 were challenged intranasally with HP-PRRSV at 28 dpv and immune and clinical parameters were monitored weekly until 49 dpv. Group 1 demonstrated significantly reduced HP-PRRSV viremia, rectal temperature and clinical scores, and significantly improved average daily weight gain (ADWG), compared to group 3. Group 2 demonstrated significantly increased IFN regulatory factor 3, stimulator of IFN genes, IFNα, and significantly decreased transforming growth factor beta (TGFβ) mRNA expressions, compared to group 1. The animals demonstrated significantly reduced HP-PRRSV viremia, but did not demonstrate any further improved PRRSV-specific antibody responses, rectal temperature, clinical scores, and ADWG as compared to group 1. Our findings suggest that quercetin up-regulates IRGs, IFNα, and down-regulates TGFβ mRNA expressions which may contribute to further reducing number of viremic pigs and HP-PRRSV viremia which were conferred by PRRSV-1 MLV vaccine. Our findings also suggest that quercetin may serve as an effective oral immunomodulator for improving cell-mediated immune defense to HP-PRRSV.
本研究评估了槲皮素对改善猪繁殖与呼吸综合征病毒-1（PRRSV-1）改良活疫苗（MLV）对高致病性（HP）-PRRSV-2攻毒的交叉保护作用的免疫调节作用。离体实验表明，槲皮素可显著增强 HP-PRRSV 感染的单核细胞衍生巨噬细胞中 I 型干扰素调节基因（IRGs）和 I 型和 II 型干扰素（IFN），并显著降低促炎和抗炎细胞因子的表达。体内实验将 4 周龄的猪（n=24）分为四组，每组 6 头。第 1 组和第 2 组在 0 dpv（接种后第 0 天）接种 PRRSV-1 MLV 疫苗。第 2 组还在 0-49 dpv 时口服给予槲皮素。第 3 组在 0 dpv 时注射 PRRSV-1 MLV 疫苗溶剂。第 4 组为严格对照。第 1-3 组在 28 dpv 时经鼻腔接种 HP-PRRSV，并在 49 dpv 前每周监测免疫和临床参数。第 1 组与第 3 组相比，HP-PRRSV 血症、直肠温度和临床评分明显降低，平均日增重（ADWG）明显提高。第 2 组与第 1 组相比，IFN 调节因子 3、IFN 基因刺激物、IFNα的表达显著增加，转化生长因子β（TGFβ）mRNA 的表达显著降低。与第 1 组相比，这些动物的 HP-PRRSV 血症明显降低，但 PRRSV 特异性抗体反应、直肠温度、临床评分和 ADWG 没有进一步改善。我们的研究结果表明，槲皮素上调 IRGs、IFNα，并下调 TGFβmRNA 表达，这可能有助于进一步减少由 PRRSV-1 MLV 疫苗引起的病毒血症猪和 HP-PRRSV 血症。我们的研究结果还表明，槲皮素可能作为一种有效的口服免疫调节剂，增强细胞介导的对 HP-PRRSV 的免疫防御。
