Faculty of Veterinary Medicine, Health Research Innovation Center 2C53, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
Department of Pathobiology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
BMC Microbiol. 2019 Feb 8;19(1):34. doi: 10.1186/s12866-019-1398-6.
Single stranded ribonucleic acid (ssRNA) binds to toll-like receptor (TLR)7 leading to recruitment of immune cells and production of pro-inflammatory cytokines, which has been shown in mammals. In chickens, synthetic ssRNA analog, resiquimod, has been shown to elicit antiviral response against infectious bursal disease virus infection. The objective of this study was to determine the innate host responses activated by the pre-hatch in ovo administration of resiquimod against infectious laryngotracheitis virus (ILTV) infection in chickens post-hatch.
First, we observed that in ovo treatment of resiquimod at embryo day (ED) 18 increases macrophage recruitment in respiratory and gastrointestinal tissues of chicken day 1 post-hatch in addition to interleukin (IL)-1β in lungs. Second, we observed that in ovo treatment of resiquimod reduces ILTV cloacal shedding at 7 days post-infection (dpi) when challenged at day 1 post-hatch coinciding with higher macrophage recruitment. In vitro, we found that resiquimod enhances production of nitric oxide (NO) and IL-1β and not type 1 interferon (IFN) activity in avian macrophages. Although, the antiviral response against ILTV is associated with the enhanced innate immune response, it is not dependent on any of the innate immune mediators observed as has been shown in vitro using avian macrophage.
This study provides insights into the mechanisms of antiviral response mediated by resiquimod, particularly against ILTV infection in chicken.
单链核糖核酸(ssRNA)与 Toll 样受体(TLR)7 结合,导致免疫细胞的募集和促炎细胞因子的产生,这在哺乳动物中已有研究。在鸡中,合成的 ssRNA 类似物瑞喹莫德已被证明能引发抗病毒反应,抵抗传染性法氏囊病病毒感染。本研究的目的是确定在孵化前对鸡胚注射瑞喹莫德,对鸡孵化后感染传染性喉气管炎病毒(ILTV)所引起的固有宿主反应。
首先,我们观察到在胚胎第 18 天(ED)对鸡胚注射瑞喹莫德,会增加孵化后第 1 天鸡呼吸道和胃肠道组织中的巨噬细胞募集,同时增加肺部的白细胞介素(IL)-1β。其次,我们观察到在孵化前对鸡胚注射瑞喹莫德,在孵化后第 1 天接种时,可减少 7 天攻毒后的 ILTV 泄殖腔脱落,同时伴随着巨噬细胞募集的增加。体外实验发现,瑞喹莫德增强了禽巨噬细胞中一氧化氮(NO)和 IL-1β的产生,而不是 1 型干扰素(IFN)的活性。尽管针对 ILTV 的抗病毒反应与增强的固有免疫反应有关,但与体外观察到的任何固有免疫介质无关,这在体外使用禽巨噬细胞中已有研究。
本研究深入了解了瑞喹莫德介导的抗病毒反应的机制,特别是对鸡传染性喉气管炎病毒感染的机制。