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在鸡胚中给予包裹在 PLGA 纳米粒中的 Toll 样受体配体可抑制马立克氏病病毒感染鸡的肿瘤发展。

In ovo administration of Toll-like receptor ligands encapsulated in PLGA nanoparticles impede tumor development in chickens infected with Marek's disease virus.

机构信息

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

出版信息

Vaccine. 2018 Jun 27;36(28):4070-4076. doi: 10.1016/j.vaccine.2018.05.091. Epub 2018 May 30.

Abstract

One of the economically important diseases in the poultry industry is Marek's disease (MD) which is caused by Marek's disease virus (MDV). The use of current vaccines provides protection against clinical signs of MD in chickens. However, these vaccines do not prevent the transmission of MDV to susceptible hosts, hence they may promote the development of new virulent strains of MDV. This issue persuaded us to explore alternative approaches to control MD in chickens. Induction of innate responses at the early stage of life in the chicken may help to prevent or reduce MDV infection. Further, prophylactic use of Toll-like receptor ligands (TLR-Ls) has been shown to generate host immunity against infectious diseases. In this regard, encapsulation of TLR-Ls in Poly(d, l-lactic-co-glycolic acid) (PLGA) may further enhance host responses by controlled release of TLR-Ls for an extended period. Hence, in the current study, protective effects of encapsulated TLR4 and TLR21 ligands, LPS and CpG, respectively, were investigated against MD. Results indicated that administration of encapsulated CpG and LPS first at embryonic day (ED) 18, followed by post-hatch at 14 days-post infection (dpi) intramuscularly, diminished tumor incidence by 60% and 42.8%, respectively at 21dpi compared to the MDV only group. In addition, analysis of cytokine gene profiles of interferon (IFN)-α, IFN-β, IFN-γ, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, IL-18 and IL-10 in spleen and bursa of Fabricius at different time points suggests that TLR-Ls possibly triggered host responses through the expression of IL-1β and IL-18 to reduce tumor formation. However, further studies are needed to explore the role of these pro-inflammatory cytokines and other influencing elements like lymphocytes in the hindrance of tumor development by TLR-Ls treatment in chickens.

摘要

家禽业中一种具有重要经济意义的疾病是马立克氏病(MD),它是由马立克氏病病毒(MDV)引起的。目前使用的疫苗可预防鸡群出现 MD 的临床症状。然而,这些疫苗并不能阻止 MDV 传播给易感宿主,因此它们可能会促进新的 MDV 强毒株的出现。这一问题促使我们探索控制鸡 MD 的替代方法。在鸡生命的早期阶段诱导先天反应可能有助于预防或减少 MDV 感染。此外,研究表明,预防性使用 Toll 样受体配体(TLR-Ls)可以产生针对传染病的宿主免疫力。在这方面,TLR-Ls 包封在聚(D,L-丙交酯-共-乙交酯)(PLGA)中可以通过延长 TLR-Ls 的释放时间来进一步增强宿主反应。因此,在本研究中,研究了分别包封的 TLR4 和 TLR21 配体 LPS 和 CpG 对 MD 的保护作用。结果表明,在胚胎第 18 天(ED)和孵化后第 14 天(感染后 14 天)分别肌内注射包封的 CpG 和 LPS,与仅 MDV 组相比,在 21 天检测时肿瘤发生率分别降低了 60%和 42.8%。此外,对不同时间点脾脏和法氏囊中干扰素(IFN)-α、IFN-β、IFN-γ、诱导型一氧化氮合酶(iNOS)、白细胞介素(IL)-1β、IL-18 和 IL-10 的细胞因子基因谱的分析表明,TLR-Ls 可能通过表达 IL-1β 和 IL-18 触发宿主反应,从而减少肿瘤形成。然而,需要进一步研究来探索这些促炎细胞因子和其他影响因素(如淋巴细胞)在 TLR-Ls 治疗鸡中抑制肿瘤发展中的作用。

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