1a. Objectives (from AD-416)
Develop proteomic profiles of immune cells during the acute and chronic stages of mastitis and under different physiologic conditions known to be associated with immune suppression, such as parturition or nutritional imbalances. Identify proteins that are up- or down-regulated during these immunosuppressive states. Initiate studies into the function of these differentially regulated proteins. Develop proteome profiles of mastitis-causing bacteria isolated from in vivo conditions and in bacteria grown in vitro or in lab counterparts that are not considered highly virulent. Identify proteins that are up- or down-regulated across bacteria studied in each ecological state and initiate studies into the role these differentially regulated proteins play in the establishment of chronic infection of the mammary gland. Studies of immunomodulators to test their effectiveness at preventing disease by imposing them on a controlled reproducible mastitis challenge model. In the course of these studies we will discover and develop immunological reagents for the bovine and relevant wildlife animal species that will facilitate the discovery of innovative immunointervention strategies.
1b. Approach (from AD-416)
The approach to this research project is through experimentation to discover new insights into the mechanisms of how the bovine dairy cow immune system fights diseases. Failure of the dairy cow immune system results in numerous diseases, of which mastitis is the predominate disease resulting in an economic burden to the industry. Our research will investigate the host immune system – pathogen interaction with the goal of enhancing immune function. To accomplish this goal we will study how immune system functions are affected by nutritional status. We will also study a newly described immune system function in the context of the dairy cow. In addition, we will investigate how pathogenic bacteria adapt to the in vivo environment and escape immune clearance. Finally, we will add to the large animal immunological reagent toolbox, to aid in study of immunological questions in dairy animals for the entire research community.
Generating Reagents/Antibodies Targeting Immunologically Important Molecules: One reason research into the functions of the immune system in domestic animals lags behind human and mouse research is the lack of reagents and antibodies. We have fragments of important immunological molecules to generate antibodies. These fragments have been used to immunize rabbits. These rabbits are in the process of receiving booster shots and are then tested for levels of antibody. These antibodies will be of importance to our research goal and will be made available to the entire research community. The impact of this research is to provide tools to the scientific community to further basic immunological research in dairy cows. This research is part of the Animal Health National Program 103, Components: Disease Control Strategies, and Genetic Resistance to Disease, as defined in the Animal Health Action Plan.
5. Significant Activities that Support Special Target Populations