Grant: Discovery Grants Program - Individual

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.