The immunological immaturity of the innate immune system during the first-week post-hatch enables pathogens to infect chickens, leading to the death of the animals. Current preventive solutions to improve the resistance of chicks to infections include vaccination, breeding, and sanitation. Other prophylactic solutions have been investigated, such as the stimulation of animal health with immunostimulants. Recent studies showed that administration of immune-modulators to one-day-old chicks, or in ovo, significantly reduces mortality in experimental bacterial or viral infection challenge models. Owing to a lack of molecular biomarkers required to evaluate chicken immune responses and assess the efficacy of vaccines or immune-modulators, challenge models are still used. One way to reduce challenge experiments is to define molecular signatures through omics approaches, resulting in new methodologies to rapidly screen candidate molecules or vaccines. This study aims at identifying a dual transcriptomics and metabolomics blood signature after administration of CpG-ODN (cytosine-phosphate-guanine oligodeoxynucleotides), a reference immune-stimulatory molecule. A clinical study was conducted with chicks and transcriptomics and metabolomics analyses were performed on whole-blood and plasma samples, respectively. Differentially expressed genes and metabolites with different abundance were identified in chicks treated with CpG-ODN. The results showed that CpG-ODN activated the innate immune system, within hours after administration, and its effect lasted over time, as metabolomics and transcriptomics profiles still varied 6 D after administration. In conclusion, through an integrated clinical omics approach, we deciphered in part the mode of action of CpG-ODN in post-hatch chicks.

中文翻译：

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新孵化雏鸡对胞嘧啶-磷酸-鸟嘌呤寡核苷酸刺激免疫反应的转录组学和代谢组学研究。

孵化后第一周内先天免疫系统的免疫学不成熟使病原体能够感染鸡，从而导致动物死亡。当前用于提高雏鸡对感染的抵抗力的预防性解决方案包括疫苗接种，繁殖和卫生。已经研究了其他预防性解决方案，例如用免疫刺激剂刺激动物健康。最近的研究表明，在一天的雏鸡或卵内施用免疫调节剂，可以大大降低实验性细菌或病毒感染挑战模型的死亡率。由于缺乏评估鸡的免疫反应和评估疫苗或免疫调节剂功效所需的分子生物标记，因此仍使用了挑战模型。减少挑战性实验的一种方法是通过组学方法定义分子特征，从而产生了快速筛选候选分子或疫苗的新方法。这项研究旨在鉴定参考免疫刺激分子CpG-ODN（胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸）给药后的双重转录组学和代谢组学血液特征。对雏鸡进行了临床研究，分别对全血和血浆样品进行了转录组学和代谢组学分析。在用CpG-ODN处理的雏鸡中鉴定出差异表达的基因和不同丰度的代谢产物。结果表明，CpG-ODN在给药后数小时内激活了先天免疫系统，其作用随时间持续，因为代谢组学和转录组学谱在给药后6 D仍变化。总之，通过综合的临床组学方法，我们部分破译了孵化后雏鸡中CpG-ODN的作用方式。