Location: Infectious Bacterial Diseases Research
Project Number: 5030-32000-221-000-D
Project Type: In-House Appropriated
Start Date: Oct 6, 2016
End Date: Oct 5, 2021
Objective 1: Identify MAP antigens including protein to protein interactions using proteomic and genomic tools to better understand their function in pathogenesis of Johne’s disease and develop improved diagnostic tools. Subobjective 1.1: Define pathogenic mechanisms of MAP through bacterial community interactions as well as protein interactions with the host. Subobjective 1.2: Detection reagents for Johne’s Disease. Objective 2: Characterize host immunity and pathogenesis of disease using immunophenotypic and cell signaling markers in response to asymptomatic and clinical MAP infection, as well as vaccination. Subobjective 2.1: Characterize patterns of Th17-mediated immune responses to natural infection in cattle in asymptomatic and clinical stages. Subobjective 2.2. Characterize key differences in host immunity upon vaccination compared to infection. Subobjective 2.3: Assess B cell mediated immunity to natural infection in cattle in asymptomatic and clinical stages using maturation and activation markers for B cell subsets. Subobjective 2.4: Characterize the impact of infection on the phenotypes of antigenpresenting cells in target tissues of infected cattle. Objective 3: Investigate genetic variability among MAP isolates of livestock using whole genome sequencing to develop improved epidemiological tools and evaluate the genetic basis of virulence. Subobjective 3.1: Identify the genotypes of MAP present in U.S. dairies using whole genome sequencing. Subobjective 3.2: Identify and characterize virulent strains of MAP.
Within Objective 1 the function of MAP proteins as antigens will be identified using genomic and proteomic tools to better understand their role(s) in pathogenesis of Johne’s Disease and to develop improved diagnostic tools. In Objective 2, tools such as cellular phenotype and secretion of cytokines involved in cell signaling will be measured to characterize host immune responses in asymptomatic and clinical stages of infection, as well after vaccination, to gain knowledge as to correlates involved in controlling the disease. Genetic variability of MAP isolates of livestock will be investigated using whole genome sequencing under Objective 3. This will lead to improved epidemiological tools in the field and understanding of MAP genes involved in virulence. The 3 major objectives outlined within this project plan will work in an interactive manner to provide us with tools to control this disease.