仔猪感染副角藻(G.副猪)诱导宿主免疫抑制。然而,仔猪免疫抑制的潜在机制仍不清楚。PD-1/PD-L1轴的激活已显示引发宿主免疫抑制。黄芩苷具有抗炎和免疫调节功能。然而,黄芩苷是否抑制PD-1/PD-L1激活,从而减轻宿主免疫抑制,目前尚未研究.在这项研究中,评价黄芩苷对猪副猪嗜血杆菌免疫抑制的作用。将70头仔猪随机分为对照组,感染组,左旋咪唑组,BMS-1组,25mg/kg黄芩苷组,50mg/kg黄芩苷组和100mg/kg黄芩苷组。用左旋咪唑预处理后,BMS-1或黄芩苷,仔猪用1×108CFU的副猪。我们的研究结果表明黄芩苷,左旋咪唑和BMS-1改变血常规指标和生化指标;下调IL-1β,IL-10,IL-18,TNF-α和IFN-γmRNA表达;并上调血液中IL-2和IL-8mRNA表达。黄芩苷,左旋咪唑和BMS-1增加了CD3+T细胞的比例,CD3+CD4+T细胞,脾细胞群中的CD3+CD8+T细胞和CD3-CD21+B细胞,增加了CD3+T细胞的比例,血液中CD3+CD4+T细胞和CD3+CD8+T细胞,并抑制PD-1/PD-L1和TIM-3的激活。黄芩苷,左旋咪唑和BMS-1降低p-PI3K,p-Akt,和p-mTOR表达式,p-MEK1/2/MEK1/2和p-ERK1/2/ERK1/2比值和RAS表达增加。黄芩苷,左旋咪唑和BMS-1对副猪氏杆菌攻击提供了实质性保护,并减轻了组织病理学损伤。我们的发现可能为控制副猪感染和其他免疫抑制疾病提供新的策略。
Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group,
levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with
levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin,
levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin,
levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3-CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin,
levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.