1a. Objectives (from AD-416):
Objective 1: Develop immune reagents to detect host effector molecules controlling immune responses and determine the role of host effector molecules in disease resistance to discover biological determinants associated with disease resistance to infectious diseases of poultry. Sub-objective 1a: Develop immune reagents to detect host effector molecules controlling immune responses to NE. Sub-objective 1b: Determine the role of host effector molecular in NE disease resistance. Objective 2: Discover effective immune intervention strategies to prevent and control infectious diseases of poultry through use of nutrients as immune modulators to enhance gut health and develop strategies for their use in increasing production efficiency. Identify effector molecules of innate immunity and develop strategies for their use in reducing economic losses associated with enteric diseases of poultry. Sub-objective 2a: Use nutrients as immune modulators to enhance gut health and develop strategies for their use in increasing production efficiency. Sub-objective 2b: Identify effector molecules of innate immunity and develop strategies for their use in reducing economic losses associated with enteric diseases of poultry.
1b. Approach (from AD-416):
Develop immune reagents to detect host effector molecules controlling immune responses. Determine the role of the host effector molecules in disease resistance. Discover biological determinants associated with disease resistance to infectious diseases of poultry.
3. Progress Report:
Under Objective 1, progress was made to develop immune reagents to identify molecules in poultry that mediate immune responses in two major infectious diseases of the intestine in poultry. Several mouse-derived monoclonal antibodies that identify biological markers of chicken dendritic cells (DCs) were developed and used to characterize DCs of poultry. Aside from this report, much less is known about the expression and function of biological markers for DCs in chicken compared with its mammalian counterpart. Using the chicken monoclonal antibodies, a putative marker that was primarily expressed on mature DCs, CD83, was identified. The chicken CD83 monoclonal antibodies will be useful for future investigations of chicken immune cell maturation and mechanisms of action. Major progress was also made in the characterization of a novel chicken immune regulating factor (cytokine) interleukin-17F, which promotes inflammation and helps maintain a stable physiological balance in the gut. In general, IL-17F cytokine is expressed when cell-mediated immunity is activated by pathogens and its expression indicates the importance of IL-17F cytokine in local immune regulation. Our study showed that upon intestinal infection with the parasites Eimeria maxima and Eimeria tenella that cause the parasitic disease Coccidiosis, the level of interleukin-17F was differentially regulated. Under Objective 2, novel antibiotic-free alternative disease control strategies against Coccidiosis and Necrotic enteritis, a parasitic and bacteria caused disease, respectively, were developed using various nutritional immune modulation strategies in collaboration with several food and nutrition companies. Our recent studies documented that the dietary immunomodulation of gut immunity in broiler chickens using natural dietary supplements and plant-derived phytochemicals that interact with innate sensing molecules to stimulate innate immunity, is a promising alternative strategy that can be applied to many infectious diseases where traditional prevention methods show limitations. In our study, we identified three plant-derived extracts that act in synergy to enhance gut immunity and protect against Coccidiosis in birds and Necrotic Enteritis in commercial broiler chickens. This finding led to the development of a commercial product for Coccidiosis. Major progress was also made in identifying specialized immune enhancing additives that increase the immune response to the Coccidiosis recombinant vaccine and provide cross protection against multiple species of the parasite Eimeria causing Coccidiosis. These additives (Montanide adjuvants: ISA 70, ISA 71, ISA 201, and ISA 206) have shown superior efficacy with a variety of human and animal vaccines. In collaboration with a private company, the effectiveness of the four additives in combination with a distinct vaccination against Coccidiosis in birds was investigated. Immunization with the profilin-based vaccine and ISA 70 or ISA 71 increased body weight gain, compared to the vaccine alone following experimental infection with the parasite Eimeria. The vaccine in combination with ISA 71 also decreased parasite survival.
Lee, S.H., Lillehoj, H.S., Jang, S.I., Lee, K., Baldwin, C., Tomkpins, D., Wagener, B., Lillehoj, E., Hong, Y. 2012. Development and characterization of mouse monoclonal antibodies reactive with chicken CD83. Veterinary Immunology and Immunopathology. 145(1-2):527-533.