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

被引:14
作者
Bavananthasivam, Jegarubee [1 ]
Alkie, Tamiru N. [1 ]
Astill, Jake [1 ]
Abdul-Careem, Mohamed Faizal [2 ]
Wootton, Sarah K. [1 ]
Behboudi, Shahriar [3 ,4 ]
Yitbarek, Alexander [1 ]
Sharif, Shayan [1 ]
机构
[1] Univ Guelph, Ontario Vet Coll, Dept Pathobiol, Guelph, ON N1G 2W1, Canada
[2] Univ Calgary, Fac Vet Med, Dept Ecosyst & Publ Hlth, Calgary, AB T2N 4N1, Canada
[3] Pirbright Inst, Ash Rd, Woking GU24 0NF, Surrey, England
[4] Univ Surrey, Sch Vet Med, Dept Pathol & Infect Dis, Guildford, Surrey, England
基金
加拿大自然科学与工程研究理事会;
关键词
Marek's disease virus; TLR ligands; Chicken embryos; In ovo administration; Cytokine genes; PLGA encapsulation; CYTOKINE GENE-EXPRESSION; T-CELLS; IMMUNOSTIMULATORY DNA; SUPPRESSION; ENHANCEMENT; RECOGNITION; GROWTH;
D O I
10.1016/j.vaccine.2018.05.091
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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)-alpha, IFN-beta, IFN-gamma, inducible nitric oxide synthase (iNOS), interleukin (IL)-1 beta, 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-I beta 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. (C) 2018 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4070 / 4076
页数:7
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