Grant: Discovery Grants Program - Individual

Oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) activate immune cells and has immense therapeutic potential in animals and human. CpG-ODN 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. We have recently compared therapeutic use of antibiotics against a single prophylactic dose of CpG-ODN in broiler chickens and found CpG-ODN was similar to therapeutic antibiotics in reducing bacterial load, and mortality against lethal bacterial infections. Although, the mechanism of innate immune protection remains elusive, we recently demonstrated innate memory or trained immunity in broiler chickens as described in in mice and humans. Innate memory or trained immunity is an intricate link between metabolism and the immune system. Moreover, recently we have demonstrated that protection broiler chickens against necrotic enteritis (NE) an intestinal disease in broiler chickens caused by Clostridium perfringens (CP) at a significant level by delivering either live or inactivated vaccine antigens of CP by the intrapulmonary route (IPL) route at hatch following administration of CpG-ODN by the in ovo route. Although the respiratory and intestinal mucosal systems have considerable variations in terms of functional role, they share anatomical similarities. Substantial evidence suggests existence of a two-way interaction between the respiratory and intestinal mucosal immune systems and this crosstalk is referred as the "gut-lung/lung-gut axis" (GLA). The GLA results from a complex interaction between the different microbial products such as short chain fatty acids, antimicrobial peptides, lipopolysaccharides, migrating immune cells and interactions of these molecules and immune cells with respective microbiome of the intestine and lung. We hypothesize that immune-metabolic interactions of multiple immune compartments play a significant role in CpG-ODN-mediated immune protection associated with the GLA concept in chickens as our short-term objective. These strategies will not only elucidate the CpG-ODN-mediated immune protective mechanisms but will also be crucial for identifying whether GLA phenomenon could be utilized with vaccine delivery in broiler chickens as our long-term goal. We will enhance the utility 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 mechanisms of CpG-ODN-mediated GLA concept in chickens. This research program has a 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.