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Combination of TLR2 and TLR3 agonists derepress infectious bursal disease virus vaccine-induced immunosuppression in the chicken

机译:TLR2和TLR3激动剂的组合可抑制鸡传染性法氏囊病病毒疫苗诱导的免疫抑制

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摘要

Live intermediate plus infectious bursal disease virus (IBDV) vaccines (hot vaccines) are used for protection against the virulent IBDV strains in young chickens. We evaluated the potential of Toll-like receptor (TLR) agonists to alleviate hot vaccine-induced immunosuppression. The combination of Pam3CSK4 and poly I:C synergistically upregulated IFN-β, IFN-γ, IL-12, IL-4, and IL-13 transcripts and cross-inhibited IL-1β, IL-10, and iNOS transcripts in the chicken peripheral blood mononuclear cells (PBMCs) as analyzed by quantitative real-time PCR. Further, four-week old specific pathogen free White Leghorn chickens (n = 60) were randomly divided into six groups and either immunized with hot IBDV vaccine with or without Pam3CSK4 and/or poly I:C or not vaccinated to serve as controls. The results indicated that poly I:C alone and in combination with Pam3CSK4 alleviated vaccine-induced immunosuppression, as evidenced by greater weight gain, increased overall antibody responses to both sheep erythrocytes and live infectious bronchitis virus vaccine, upregulated IFN-γ transcripts and nitric oxide production by PBMCs (P < 0.05), and lower bursal lesion score in the experimental birds. In conclusion, poly I:C alone and its combination with Pam3CSK4 reduced the destruction of B cells as well as bursal damage with restoration of function of T cells and macrophages when used with a hot IBDV vaccine.
机译:活的中间加传染性法氏囊病病毒(IBDV)疫苗(热疫苗)用于预防雏鸡中的强毒IBDV毒株。我们评估了Toll样受体(TLR)激动剂缓解热疫苗诱导的免疫抑制的潜力。 Pam3CSK4和poly I:C的组合可协同上调鸡中的IFN-β,IFN-γ,IL-12,IL-4和IL-13转录本以及交叉抑制的IL-1β,IL-10和iNOS转录本通过定量实时PCR分析的外周血单核细胞(PBMC)。此外,将四周龄的无特定病原体的白来亨鸡(n = 60)随机分为六组,并用带有或不带有Pam3CSK4和/或poly I:C的热IBDV疫苗进行免疫,或者不进行疫苗接种作为对照。结果表明,单独的Poly I:C以及与Pam3CSK4联合使用可减轻疫苗诱导的免疫抑制,如体重增加更大,对绵羊红血球和活的传染性支气管炎病毒疫苗的总体抗体反应增加,IFN-γ转录物和一氧化氮上调的证据PBMCs产生(P <0.05),且实验鸟的法氏囊病变评分更低。总之,当与热IBDV疫苗一起使用时,单独的poly I:C及其与Pam3CSK4的结合减少了B细胞的破坏以及法氏囊损伤,同时恢复了T细胞和巨噬细胞的功能。

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