Annamalai Arunsaravanakumar, Ramakrishnan Saravanan, Sachan Swati, Kumar B S Anand, Sharma Bal Krishan, Kumar Vimal, Palanivelu Munuswamy, Varghese Berin P, Kumar Ajay, Saravanan B C, Krishnaswamy Narayanan
Immunology Section, IVRI, Izatnagar, Bareilly, Uttar Pradesh 243 122, India.
Immunology Section, IVRI, Izatnagar, Bareilly, Uttar Pradesh 243 122, India.
Vet Microbiol. 2016 May 1;187:21-30. doi: 10.1016/j.vetmic.2016.03.005. Epub 2016 Mar 9.
The study evaluated the prophylactic potential of resiquimod (R-848), a synthetic TLR7 agonist, against very virulent infectious bursal disease virus (vvIBDV) infection in chicken. Specific pathogen free White Leghorn chicks of three week age were treated with R-848 (50μg/bird, intramuscular) or PBS (n=26/group). Twenty four hour later, half of the birds from each group were challenged with 10(5) ELD50 of vvIBDV and observed for 10days. To understand the effect of R-848, immune response genes such as interferon (IFN)-β, IFN-γ, IL-1β, IL-4, iNOS and TLR7 were analyzed at 24 and 48h post-challenge in PBMCs ex vivo by real-time PCR (n=6/group). On day 4 post-challenge, representative birds (n=3/group) were sacrificed to study the bursal damage and IBDV antigen clearance. Immunosuppression was assessed by antibody response against live Newcastle disease virus (NDV) vaccine, which was administered on day 10 post-challenge. R-848 pre-treatment significantly upregulated the transcripts of each immune response gene studied (P<0.05). There was 50% mortality on vvIBDV challenge in control birds, while it was only 20% with R-848 group. R-848 pre-treatment reduced the bursal damage as indicated by lower bursal lesion score in histopathology, reduced IBDV antigen signal in immunohistochemistry and improved antigen clearance in agar gel immunodiffusion test. Further, it protected significantly against vvIBDV induced immunosuppression as indicated by HI antibody titre. It is concluded that pre-treatment of R-848 conferred partial protection from mortality and bursal damage while complete protection against immunosuppression in chicken when challenged with vvIBDV, which could be due to the upregulation of immune response genes.
该研究评估了合成的Toll样受体7(TLR7)激动剂瑞喹莫德(R - 848)对鸡高致病性传染性法氏囊病病毒(vvIBDV)感染的预防潜力。用R - 848(50μg/只,肌肉注射)或磷酸盐缓冲液(PBS)处理3周龄的无特定病原体白来航鸡雏(每组n = 26只)。24小时后,每组一半的鸡用10⁵ELD₅₀的vvIBDV进行攻毒,并观察10天。为了解R - 848的作用,在攻毒后24小时和48小时,通过实时PCR对体外外周血单核细胞(PBMCs)中的免疫反应基因如干扰素(IFN)-β、IFN-γ、白细胞介素(IL)-1β、IL-4、诱导型一氧化氮合酶(iNOS)和TLR7进行分析(每组n = 6只)。攻毒后第4天,处死代表性鸡只(每组n = 3只)以研究法氏囊损伤和IBDV抗原清除情况。通过针对活新城疫病毒(NDV)疫苗的抗体反应评估免疫抑制,该疫苗在攻毒后第10天接种。R - 848预处理显著上调了所研究的每个免疫反应基因的转录本(P<0.05)。对照鸡在vvIBDV攻毒后的死亡率为50%,而R - 848组仅为20%。R - 848预处理降低了法氏囊损伤,组织病理学显示法氏囊病变评分较低,免疫组织化学显示IBDV抗原信号减少,琼脂凝胶免疫扩散试验显示抗原清除改善。此外,如血凝抑制(HI)抗体效价所示,它对vvIBDV诱导的免疫抑制有显著保护作用。得出结论,R - 848预处理在鸡受到vvIBDV攻毒时可提供部分保护以降低死亡率和法氏囊损伤,同时对免疫抑制提供完全保护,这可能是由于免疫反应基因的上调所致。