Oligodeoxynucleotides containing CpG motifs (CpG-ODN) as an innate immune stimulator in broiler chickens

含有 CpG 基序的寡脱氧核苷酸 (CpG-ODN) 作为肉鸡先天免疫刺激剂

• 批准号: RGPIN-2018-06502
• 负责人: Gomis, Susantha
• 金额: $ 6.12万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=766045
• 关键词: Oligodeoxynucleotides; containing; CpG; motifs; ODN

Oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) activate immune cells and induce cytokine secretion. CpG-ODN has immense therapeutic potential in animal and human health and is a promising alternative to antibiotic use in the poultry industry, helping prevent the emergence of antibiotic-resistant superbugs. We reported for the first time that CpG-ODN alone can provide protective immunity against bacterial infections without vaccines or antibiotics. However, the mechanisms for such innate immune protection remains elusive. Studies are needed to understand the factors that orchestrate CpG-ODN regulated training of innate immunity leading to the host defense against pathogens. Several recent studies in mice and humans demonstrated an intricate link between metabolism and the immune system. Immune-metabolic interaction studies demonstrated the crucial roles of metabolic reprogramming in immune cell differentiation, proliferation, and function. Metabolic signature molecules have been discovered to predict the outcomes of immunity or diseases. Recently, using ultra-high pressure liquid chromatography-mass spectroscopy, we profiled metabolites in the serum and organs of CpG-ODN or saline-treated chickens. Interestingly, we found that CpG-ODN treatment significantly changes the metabolic profiles, increasing the molecules implicated in enhanced immune cell function, as in mice and humans. We hypothesize that immune-metabolic interaction plays a significant role in CpG-ODN-mediated protection in chickens. The short term objectives of the proposed research program will identify a holistic view of CpG-ODN-mediated protective immunity, by investigating the events occurring in various immune compartments and the ensuing cellular metabolic processes. Cellular activation and differentiation of immune cells, including dendritic cells, macrophages, T-cells, and cytokine-chemokine profiles, will be studied in different immune compartments. Immune cells will be sorted based on immune activation markers and costimulatory molecules for RNA sequencing analysis in conjunction with immune function, metabolomics, and cellular metabolic assays. These strategies will not only dissect the CpG-ODN-mediated immune protective mechanisms but will also be crucial for identifying whether the innate immune memory phenomenon, as reported in mice and humans, also exists in chickens. Our long-term goal is to optimize the use of CpG-ODN as an alternative to antibiotics in the poultry industry to ensure safe poultry products for consumers. This novel, innovative research will provide much basic information on the mechanisms of CpG-ODN-mediated immune protection in chickens. This program has great scope for HQP training in cutting-edge research, and the data generated will have a huge impact on the CpG-ODN research field for veterinary and human applications.

含有未甲基化 CpG 基序 (CpG-ODN) 的寡脱氧核苷酸可激活免疫细胞并诱导细胞因子分泌。 CpG-ODN 在动物和人类健康方面具有巨大的治疗潜力，是家禽业中抗生素使用的有前途的替代品，有助于防止抗生素耐药性超级细菌的出现。我们首次报道，单独使用 CpG-ODN 即可提供针对细菌感染的保护性免疫力，无需疫苗或抗生素。然而，这种先天免疫保护的机制仍然难以捉摸。需要研究来了解协调 CpG-ODN 调节的先天免疫训练导致宿主防御病原体的因素。 最近对小鼠和人类的几项研究表明，新陈代谢和免疫系统之间存在着复杂的联系。免疫代谢相互作用研究证明了代谢重编程在免疫细胞分化、增殖和功能中的关键作用。已发现代谢特征分子可以预测免疫或疾病的结果。最近，我们利用超高压液相色谱-质谱法分析了 CpG-ODN 或盐水处理鸡的血清和器官中的代谢物。有趣的是，我们发现 CpG-ODN 治疗显着改变了代谢特征，增加了与增强免疫细胞功能有关的分子，就像在小鼠和人类中一样。我们假设免疫代谢相互作用在 CpG-ODN 介导的鸡保护中发挥重要作用。拟议研究计划的短期目标将通过研究各种免疫区室中发生的事件以及随后的细胞代谢过程，确定 CpG-ODN 介导的保护性免疫的整体观点。将在不同的免疫区室中研究免疫细胞（包括树突状细胞、巨噬细胞、T 细胞和细胞因子趋化因子谱）的细胞活化和分化。将根据免疫激活标记和共刺激分子对免疫细胞进行分类，以进行 RNA 测序分析，并结合免疫功能、代谢组学和细胞代谢测定。这些策略不仅将剖析 CpG-ODN 介导的免疫保护机制，而且对于确定小鼠和人类中报道的先天免疫记忆现象是否也存在于鸡中至关重要。我们的长期目标是在家禽业中优化使用 CpG-ODN 作为抗生素的替代品，以确保消费者获得安全的家禽产品。这项新颖、创新的研究将为 CpG-ODN 介导的鸡免疫保护机制提供大量基础信息。该项目为尖端研究领域的HQP培训提供了广阔的空间，产生的数据将对CpG-ODN研究领域的兽医和人类应用产生巨大影响。